Centre for Human Drug Research - CHDR.nl http://www.chdr.nl Het laatste nieuws van CHDR Copyright 2012CHDR 2012-07-03T17:26:52+02:00 CHDR at EPHAR July 17-20, 2012 http://www.chdr.nl/default.asp?id=778&nieuwsid=163 If you plan to be there, don't miss the opportunity to meet with the CHDR team,
dr. Ingrid de Visser and Lenneke Schrier at the poster presentation:


"Evaluation of a new optical imaging agent for c-Met in healthy volunteers
and subjects with high suspicion of colorectal cancer".

]]> If you plan to be there, don't miss the opportunity to meet with the CHDR team,
dr. Ingrid de Visser and Lenneke Schrier at the poster presentation:


"Evaluation of a new optical imaging agent for c-Met in healthy volunteers
and subjects with high suspicion of colorectal cancer".

]]> 2012-07-03T17:26:52+02:00 CHDR Education Newsletter June 2012 http://www.chdr.nl/default.asp?id=778&nieuwsid=162

CHDR Education Newsletter June 2012


The TRC application TRC Pharmacology database now available as TRC app for iPad
The Centre of Human Drug Research and the Leiden University Medical Centre are proudly presenting the brand new Teaching Resource Centre (TRC) Pharmacology app as the newest teaching technology. The TRC iPad app is now available to download for free from the app-store. The convenient usage of the TRC app is a further step in the development of high-end teaching material. The TRC is the system for pharmacology teaching developed as part of CHDR’s educational mission.

Features of the TRC app

  • Peer-reviewed information on basic pharmacology and system (organ) specific pharmacology
  • Thorough explanation of pharmacological mechanisms of action based on (patho-) physiology
  • Consistent graphics using the TRC symbols
  • Up-to-date pharmacological and pharmacotherapeutic information
  • Knowledge assessment with immediate feedback
  • Links to drug formularies and other drug or disease specific guidelines
  • Built-in search function
  • Free download of the entire TRC Pharmacology database
  • Fully operational offline with automatic updates
Currently, the app is available for the iPad and it is in development for other tablets (android systems) and phones (iPhone and smart phones).

Screenshots of the TRC appScreenshots of the TRC app 

Download now the free TRC app using the following link.


About the TRC website
The TRC is a pharmacology database website that is freely available to all educators and students worldwide. Based upon the physiology and pathophysiology the pharmacological mechanisms are illustrated schematically with the icon language and are supported by explanatory text. Students can assess their gained knowledge with multiple choice questions including feedback on the answers. The TRC is initially created for Leiden Medical students, but in the last year has become more popular nationally (Maastricht students) and abroad (students of Manchester University medical school (UK) and University of Colorado (USA)).

Besides the drug mechanisms, the TRC also explains basic pharmacodynamic and -kinetic principles. For the application of the pharmacological knowledge, the students can practice writing therapeutic plans according the 6STEP methodology on the TRC website. About 40 cases are available with different stages of complexity; from beginners towards advanced cases. The TRC has different user-friendly functionalities such as personalization (each user has its own TRC page), search function, and 6STEP portfolio. These learning strategies are offered as a service to course coordinators and thus promote cooperation. The TRC database can be viewed at http://coo.lumc.nl/TRC after creating an account for free at www.medicaleducation.nl .

We hope that the new TRC app for the iPad will contribute to improved access to pharmacological information, better learning strategies, better student and physician performance and ultimately better patient care.

Please try the TRC app and give us feedback for improvements (trc@chdr.nl).

The TRC-team

Adam Cohen
Eline Dubois
Joop van Gerven
Robert Rissmann

Whatch the new CHDR grow Contact us: 

Robert Rissmann, PhD
Director of Education
Centre for Human Drug Research
Zernikedreef 10, 2333 CL Leiden
The Netherlands
trc@chdr.nl
www.chdr.nl




]]>

CHDR Education Newsletter June 2012


The TRC application TRC Pharmacology database now available as TRC app for iPad
The Centre of Human Drug Research and the Leiden University Medical Centre are proudly presenting the brand new Teaching Resource Centre (TRC) Pharmacology app as the newest teaching technology. The TRC iPad app is now available to download for free from the app-store. The convenient usage of the TRC app is a further step in the development of high-end teaching material. The TRC is the system for pharmacology teaching developed as part of CHDR’s educational mission.

Features of the TRC app

  • Peer-reviewed information on basic pharmacology and system (organ) specific pharmacology
  • Thorough explanation of pharmacological mechanisms of action based on (patho-) physiology
  • Consistent graphics using the TRC symbols
  • Up-to-date pharmacological and pharmacotherapeutic information
  • Knowledge assessment with immediate feedback
  • Links to drug formularies and other drug or disease specific guidelines
  • Built-in search function
  • Free download of the entire TRC Pharmacology database
  • Fully operational offline with automatic updates
Currently, the app is available for the iPad and it is in development for other tablets (android systems) and phones (iPhone and smart phones).

Screenshots of the TRC appScreenshots of the TRC app 

Download now the free TRC app using the following link.


About the TRC website
The TRC is a pharmacology database website that is freely available to all educators and students worldwide. Based upon the physiology and pathophysiology the pharmacological mechanisms are illustrated schematically with the icon language and are supported by explanatory text. Students can assess their gained knowledge with multiple choice questions including feedback on the answers. The TRC is initially created for Leiden Medical students, but in the last year has become more popular nationally (Maastricht students) and abroad (students of Manchester University medical school (UK) and University of Colorado (USA)).

Besides the drug mechanisms, the TRC also explains basic pharmacodynamic and -kinetic principles. For the application of the pharmacological knowledge, the students can practice writing therapeutic plans according the 6STEP methodology on the TRC website. About 40 cases are available with different stages of complexity; from beginners towards advanced cases. The TRC has different user-friendly functionalities such as personalization (each user has its own TRC page), search function, and 6STEP portfolio. These learning strategies are offered as a service to course coordinators and thus promote cooperation. The TRC database can be viewed at http://coo.lumc.nl/TRC after creating an account for free at www.medicaleducation.nl .

We hope that the new TRC app for the iPad will contribute to improved access to pharmacological information, better learning strategies, better student and physician performance and ultimately better patient care.

Please try the TRC app and give us feedback for improvements (trc@chdr.nl).

The TRC-team

Adam Cohen
Eline Dubois
Joop van Gerven
Robert Rissmann

Whatch the new CHDR grow Contact us: 

Robert Rissmann, PhD
Director of Education
Centre for Human Drug Research
Zernikedreef 10, 2333 CL Leiden
The Netherlands
trc@chdr.nl
www.chdr.nl




]]> 2012-06-20T17:26:52+02:00 Newsletter June 2012 http://www.chdr.nl/default.asp?id=778&nieuwsid=161

CHDR Newsletter June 2012

 


Meet CHDR at Bio Boston, June 18-21, 2012
CHDR is attending the annual BIO convention in Boston, June 18-21, 2012. If you plan to be there, don't miss the opportunity to meet with the CHDR team:

Koos Burggraaf
Since 1990 he has held several positions at the Centre for Human Drug Research where he also obtained his PhD in 1998. His main focus of interest has been on early drug development (phase I/II), with special emphasis on biologicals, including method development (in particular in cardiovascular medicine, endocrinology, endothelial function, inflammation, gastrointestinal function), and pediatric drug research.

 

Joop van Gerven
Since 1994 he is director CNS research at the Centre for Human Drug Research (CHDR) in Leiden, and is responsible for consultancy and research on central nervous system drugs and methods. His primary interest is in the prediction of pharmacological effects of CNS-active agents during early phases of drug development, and in neuropsychiatric challenge-tests.

  

Trials & techniques

Controlled noise simulation in sleep lab
CHDR's sleep facility is well known for its possibilities to test multimodal functionalities of sleep including polysomnography (PSG), Neurocart CNS testing and/or blood sampling throughout the night. We recently added the option of controlled noise simulation. Noise simulations may be useful to either mimic the effects of environmental noise on sleep quality, or as a method of intentionally disturbing sleep in a controlled manner and testing the efficacy of (new) sleeping agents in overcoming the noise induced sleep disturbance. Using a noise model in healthy volunteers rather than patients to test novel potential sleep agents greatly increases efficiency and cost of such clinical trials.

Cognition and attention perturbation with mecamylamine
In addition to the anti-muscarinic scopolamine challenge model that we developed to induce temporary cognitive deficits, we are currently performing a trial with mecamylamine, a nicotinergic acetylcholine receptor antagonist. The aim of the present study is to set-up an anti-cholinergic challenge method in healthy volunteers in order to better prove pharmacology of nicotinergic agonists that are currently in development for symptomatic treatment of Alzheimer's disease. Different doses of mecamylamine are tested and thorough pharmacokinetic and pharmacodynamic profiling is performed in comparison to scopolamine and placebo.

Resting state fMRI in patients with dementia
CHDR continues its collaboration with the Leiden Institute for Brain and Cognition in a new study investigating the effects of a single dose of galantamine or citalopram on brain resting state networks using pharmaco-functional MRI (ph-rs-fMRI). Resting state fMRI is being investigated as an early diagnostic tool for neurodegenerative disorders. The serotonergic and cholinergic systems are known to be differentially affected in different types of dementia. Rs-fMRI with a pharmacologic challenge using a serotonergic (citalopram) and cholinergic (galantamine) drug, therefore, may also help in distinguishing the type of dementia. Patients with mild forms of Alzheimer's or fronto-temporal dementia or dementia with Lewy bodies will be included in this cross-over, placebo controlled study. In addition, by including both young and elderly healthy participants in the control group, the effects of normal aging on resting state networks will be addressed.

Publications, posters & presentations

Placebo- and amitriptyline-controlled evaluation of central nervous system effects of the NK1 receptor antagonist aprepitant and intravenous alcohol infusion
Recent interest in NK1 receptor antagonists has focused on a potential role in the treatment of drug addiction and substance abuse. In the present study, the potential for interactions between the NK1 receptor antagonist aprepitant and alcohol was evaluated. Amitriptyline was included as a positive control for the pharmacodynamic tests.

Hydrolyzed casein decreases postprandial glucose concentrations in T2DM patients irrespective of leucine content.
Geerts BF, van Dongen MG, Flameling B, Moerland MM, de Kam ML, Cohen AF, Romijn JA, Gerhardt CC, Kloek J, Burggraaf J.
J Diet Suppl. 2011; 8: 280-292
A trial to compare the effects of a single meal replacement on postprandial serum glucose, insulin, and glucagon was performed in 36 T2DM patients who continued their oral anti-diabetic medication. Each patient received three out of four treatments: a proprietary casein hydrolysate (insuVida™) alone or with additional leucine, unhydrolyzed casein, or placebo. A single dose of insuVida™ with or without addition of leucine significantly lowered plasma glucose compared to placebo and intact casein in T2DM patients.

First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development.
Strougo A, Eissing T, Yassen A, Willmann S, Danhof M, Freijer J.
J Pharmacokinet Pharmacodyn. 2012; 39: 195-203Ratio of clearance predictions using AS in combination with maturation function to clearance predictions using PBPK models
Dose selection for "first in children" trials often relies on scaling of the pharmacokinetics from adults to children. A comparison of physiologically-based pharmacokinetic modeling (PBPK) and allometric scaling (AS) provides insight that AS maturation functions do not solely represent ontogeny of enzyme activity, but aggregate multiple pharmacokinetic properties, as for example extraction ratio and lipophilicity (log P) and predictions using AS in combination with maturation functions and PBPK were not interchangeable. This highlights the necessity of investigating methodological uncertainty to allow a proper estimation of the "first dose in children" and assessment of its risk and benefits.

Re-engineering the European Union Clinical Trials Directive
Kenter MJ, Cohen AF.
Lancet 2012;379:1765-1769
The European Union Clinical Trials Directive 2001/20/EC (EU CTD), which was introduced in 2004 for drug trials, aims to protect European citizens who take part in research, safeguard data quality, and harmonise the review of clinical trials. Unfortunately, the directive is based on an ill-defined, two-tier assessment system in which two review bodies—a national competent authority and a research ethics committee (REC)—both evaluate the same clinical trial application in every member state. The European Commission is currently considering a revision of the EU CTD, but before changing the current regulations, a fundamental discussion is needed about how European citizens who take part in health research can be protected without jeopardising medical progress.

Six months treatment with ibopamine in patients with hypotony after vitreoretinal surgery for retinal detachment, uveitis or penetrating trauma
Ganteris-Gerritsen E, Ugahary LC, Jansen J, Mulder PG, Cohen AF, van Meurs JC.
retina 2012 ;32:742-747.
This study confirms that the use of topical ibopamine may result in a sustained increase in intraocular pressure of >2 mmHg in the majority of patients, but was only well tolerated in half of them. There may only be a few patients, however, who will clinically benefit from this rise in intraocular pressure. A better formulation or method of administration would be needed.


Whatch the new CHDR growContact us:
Marieke van den Bosch
Business Development manager
+31-71-5246487
bd@chdr.nl
www.chdr.nl

 

]]>

CHDR Newsletter June 2012

 


Meet CHDR at Bio Boston, June 18-21, 2012
CHDR is attending the annual BIO convention in Boston, June 18-21, 2012. If you plan to be there, don't miss the opportunity to meet with the CHDR team:

Koos Burggraaf
Since 1990 he has held several positions at the Centre for Human Drug Research where he also obtained his PhD in 1998. His main focus of interest has been on early drug development (phase I/II), with special emphasis on biologicals, including method development (in particular in cardiovascular medicine, endocrinology, endothelial function, inflammation, gastrointestinal function), and pediatric drug research.

 

Joop van Gerven
Since 1994 he is director CNS research at the Centre for Human Drug Research (CHDR) in Leiden, and is responsible for consultancy and research on central nervous system drugs and methods. His primary interest is in the prediction of pharmacological effects of CNS-active agents during early phases of drug development, and in neuropsychiatric challenge-tests.

  

Trials & techniques

Controlled noise simulation in sleep lab
CHDR's sleep facility is well known for its possibilities to test multimodal functionalities of sleep including polysomnography (PSG), Neurocart CNS testing and/or blood sampling throughout the night. We recently added the option of controlled noise simulation. Noise simulations may be useful to either mimic the effects of environmental noise on sleep quality, or as a method of intentionally disturbing sleep in a controlled manner and testing the efficacy of (new) sleeping agents in overcoming the noise induced sleep disturbance. Using a noise model in healthy volunteers rather than patients to test novel potential sleep agents greatly increases efficiency and cost of such clinical trials.

Cognition and attention perturbation with mecamylamine
In addition to the anti-muscarinic scopolamine challenge model that we developed to induce temporary cognitive deficits, we are currently performing a trial with mecamylamine, a nicotinergic acetylcholine receptor antagonist. The aim of the present study is to set-up an anti-cholinergic challenge method in healthy volunteers in order to better prove pharmacology of nicotinergic agonists that are currently in development for symptomatic treatment of Alzheimer's disease. Different doses of mecamylamine are tested and thorough pharmacokinetic and pharmacodynamic profiling is performed in comparison to scopolamine and placebo.

Resting state fMRI in patients with dementia
CHDR continues its collaboration with the Leiden Institute for Brain and Cognition in a new study investigating the effects of a single dose of galantamine or citalopram on brain resting state networks using pharmaco-functional MRI (ph-rs-fMRI). Resting state fMRI is being investigated as an early diagnostic tool for neurodegenerative disorders. The serotonergic and cholinergic systems are known to be differentially affected in different types of dementia. Rs-fMRI with a pharmacologic challenge using a serotonergic (citalopram) and cholinergic (galantamine) drug, therefore, may also help in distinguishing the type of dementia. Patients with mild forms of Alzheimer's or fronto-temporal dementia or dementia with Lewy bodies will be included in this cross-over, placebo controlled study. In addition, by including both young and elderly healthy participants in the control group, the effects of normal aging on resting state networks will be addressed.

Publications, posters & presentations

Placebo- and amitriptyline-controlled evaluation of central nervous system effects of the NK1 receptor antagonist aprepitant and intravenous alcohol infusion
Recent interest in NK1 receptor antagonists has focused on a potential role in the treatment of drug addiction and substance abuse. In the present study, the potential for interactions between the NK1 receptor antagonist aprepitant and alcohol was evaluated. Amitriptyline was included as a positive control for the pharmacodynamic tests.

Hydrolyzed casein decreases postprandial glucose concentrations in T2DM patients irrespective of leucine content.
Geerts BF, van Dongen MG, Flameling B, Moerland MM, de Kam ML, Cohen AF, Romijn JA, Gerhardt CC, Kloek J, Burggraaf J.
J Diet Suppl. 2011; 8: 280-292
A trial to compare the effects of a single meal replacement on postprandial serum glucose, insulin, and glucagon was performed in 36 T2DM patients who continued their oral anti-diabetic medication. Each patient received three out of four treatments: a proprietary casein hydrolysate (insuVida™) alone or with additional leucine, unhydrolyzed casein, or placebo. A single dose of insuVida™ with or without addition of leucine significantly lowered plasma glucose compared to placebo and intact casein in T2DM patients.

First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development.
Strougo A, Eissing T, Yassen A, Willmann S, Danhof M, Freijer J.
J Pharmacokinet Pharmacodyn. 2012; 39: 195-203Ratio of clearance predictions using AS in combination with maturation function to clearance predictions using PBPK models
Dose selection for "first in children" trials often relies on scaling of the pharmacokinetics from adults to children. A comparison of physiologically-based pharmacokinetic modeling (PBPK) and allometric scaling (AS) provides insight that AS maturation functions do not solely represent ontogeny of enzyme activity, but aggregate multiple pharmacokinetic properties, as for example extraction ratio and lipophilicity (log P) and predictions using AS in combination with maturation functions and PBPK were not interchangeable. This highlights the necessity of investigating methodological uncertainty to allow a proper estimation of the "first dose in children" and assessment of its risk and benefits.

Re-engineering the European Union Clinical Trials Directive
Kenter MJ, Cohen AF.
Lancet 2012;379:1765-1769
The European Union Clinical Trials Directive 2001/20/EC (EU CTD), which was introduced in 2004 for drug trials, aims to protect European citizens who take part in research, safeguard data quality, and harmonise the review of clinical trials. Unfortunately, the directive is based on an ill-defined, two-tier assessment system in which two review bodies—a national competent authority and a research ethics committee (REC)—both evaluate the same clinical trial application in every member state. The European Commission is currently considering a revision of the EU CTD, but before changing the current regulations, a fundamental discussion is needed about how European citizens who take part in health research can be protected without jeopardising medical progress.

Six months treatment with ibopamine in patients with hypotony after vitreoretinal surgery for retinal detachment, uveitis or penetrating trauma
Ganteris-Gerritsen E, Ugahary LC, Jansen J, Mulder PG, Cohen AF, van Meurs JC.
retina 2012 ;32:742-747.
This study confirms that the use of topical ibopamine may result in a sustained increase in intraocular pressure of >2 mmHg in the majority of patients, but was only well tolerated in half of them. There may only be a few patients, however, who will clinically benefit from this rise in intraocular pressure. A better formulation or method of administration would be needed.


Whatch the new CHDR growContact us:
Marieke van den Bosch
Business Development manager
+31-71-5246487
bd@chdr.nl
www.chdr.nl

 

]]> 2012-06-12T17:26:52+02:00 Hoogste punt CHDR gebouw bereikt http://www.chdr.nl/default.asp?id=778&nieuwsid=160 CHDR verricht onderzoek naar de effecten van nieuwe geneesmiddelen bij patiënten en gezonde proefpersonen voor farmaceutische industrieën vanuit de hele wereld en werkt samen met het LUMC. In CHDR worden ook promovendi en studenten van de UL opgeleid.  De nieuwe onderzoeksafdeling is een van de grootste van Europa en een van de weinigen in de wereld geassocieerd met een universiteit.

De directeur van CHDR, Prof dr Adam Cohen stipte nog eens het belang van goed geneesmiddelonderzoek aan om snel en efficiënt zorg te dragen voor het beschikbaar komen van geneesmiddelen voor de ziektes waar nog geen goede behandelingen voor zijn.

Nadere inlichtingen bij:

Marieke van den Bosch
Business development manager van CHDR
071-5246400
bd@chdr.nl
http://www.chdr.nl

CEPEZED
http://www.cepezed.nl/

Leiden Bio Science Park
http://www.leidenbiosciencepark.nl/

DuPrie
http://www.duprie.nl

]]> CHDR verricht onderzoek naar de effecten van nieuwe geneesmiddelen bij patiënten en gezonde proefpersonen voor farmaceutische industrieën vanuit de hele wereld en werkt samen met het LUMC. In CHDR worden ook promovendi en studenten van de UL opgeleid.  De nieuwe onderzoeksafdeling is een van de grootste van Europa en een van de weinigen in de wereld geassocieerd met een universiteit.

De directeur van CHDR, Prof dr Adam Cohen stipte nog eens het belang van goed geneesmiddelonderzoek aan om snel en efficiënt zorg te dragen voor het beschikbaar komen van geneesmiddelen voor de ziektes waar nog geen goede behandelingen voor zijn.

Nadere inlichtingen bij:

Marieke van den Bosch
Business development manager van CHDR
071-5246400
bd@chdr.nl
http://www.chdr.nl

CEPEZED
http://www.cepezed.nl/

Leiden Bio Science Park
http://www.leidenbiosciencepark.nl/

DuPrie
http://www.duprie.nl

]]> 2012-04-27T17:26:52+02:00 CHDR Newsletter March 2012 http://www.chdr.nl/default.asp?id=778&nieuwsid=158

CHDR Newsletter March 2012

 

Promasys Newsletter
In February 2012 Promasys launched a new version of a clinical data management and EDC software suite. Furthermore it unveils some features of the future Promasys iPad app.
More information

Bio-Europe Spring Amsterdam, The Netherlands: March 19-21, 2012
The annual international partnering conference, the Bio-Europe Spring will take place in Amsterdam. Together with our partner ABL, CHDR will be present at the event with a stand where our senior consultants will be available for discussions and meetings. In addition, CHDR’s partner organization in the US, CATO Research will join us and together we will be available to present our package of complimentary services. Feel free to visit us at the conference and meet with our consultants in drug development.
Further information on the BIO meeting

Side event Bio-Europe Spring: Life sciences community in Leiden
Following the BIO-Europe, on Thursday 22 March, the Medical Delta & Leiden Bio Science Park the offer the opportunity to get acquainted with the unique life sciences community in Leiden and arrange a visit to the park. The visit will include presentations, field visits to research sites or companies as well as ample networking opportunities. All side visits include transportation from Amsterdam to the side event location and back.
Read more

Side event Bio-Europe Spring: Alzheimer Center
Life Sciences Center Amsterdam is proudly hosting a lightning session entitled ‘Drug Development, Imaging, and Clinical Trials in Alzheimer Disease’, chaired by Dr. Philip Scheltens, Director of the Alzheimer Center at Amsterdam’s VU University Medical Center (VUmc).
Read more


Trials & Techniques

Induction of psychomimetic symptoms with ketamine
In addition to the THC-challenge model that we are developing for psychosis (Liem-Moolenaar et al. 2010, Kleinloog et al. submitted), we performed a trial where S(+)-ketamine was used to induce psychomimetic symptoms as a potential model for psychosis and antipsychotic drug action. Different target concentrations were tested and we found that ketamine can induce a robust, dose-dependent increase on different subscales of the Positive and Negative Syndrome Scale (PANSS) and different tests of the NeuroCart (e.g. smooth pursuit eye movements, adaptive tracking). Although many (side-)effects of ketamine were observed, these were mostly mild and dose-related.
Daniël Kleinloog

Population for Drug Abuse Liability studies
CHDR has performed many studies where healthy volunteers who had to be mild cannabis users were recruited. The subjects in these studies were compared to subjects who participated in other studies, to assess their suitability as a population for drug abuse liability studies. Mild cannabis users were found to be more flexible and open to new experiences than other healthy volunteers. They are also somewhat less cooperative and adherent to social standards, which was associated with a mildly reduced compliance to study procedures. Our experience with recruiting mild cannabis users, the different personality traits and a compliance to study procedures that is expected to be improved compared to a population of polydrug abusers (current standard drug abuse liability studies) makes a strong argument for the use of mild cannabis users in drug abuse liability studies.
Daniël Kleinloog

Posters, Presentations & Publications

PhD-Thesis: Human pharmacology of current and new treatments for schizophrenia
At the 8th of March Marieke Liem-Moolenaar successfully defended her PhD thesis "Human pharmacology of current and new treatments for schizophrenia".
Together, the studies described in this thesis give an impression of the current drug development in schizophrenia, show different ways of studying human pharmacology and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers.
Download Thesis or Recieve a Hardcopy
Marieke Liem-Moolenaar


Involvement of the endocannabinoid system in reward processing in the human brain.
van Hell HH, Jager G, Bossong MG, Brouwer A, Jansma JM, Zuurman L, van Gerven J, Kahn RS, Ramsey NF.
Psychopharmacology (Berl). 2012; 219: 981-990
fMRI has been used to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ(9)-tetrahydrocannabinol (THC) on reward-related brain activity. Results suggest a role for the eCB system in the appreciation of rewards.

Pharmacokinetics and central nervous system effects of the novel dopamine D3 receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-steady state.
Te Beek ET, Zoethout RW, Bani MS, Andorn A, Iavarone L, Klaassen ES, Fina P, van Gerven JM.
J Psychopharmacol. 2012; 26: 303-314
 In a blinded, randomized, placebo-controlled study, effects of a single oral dose of a novel dopamine D3 receptor antagonist were evaluated in healthy volunteers. Pharmacokinetics, central nervous system (CNS) effects and potential for interaction with alcohol were evaluated, using an alcohol infusion paradigm and CHDR’s NeuroCart CNS test battery. After co-administration with alcohol, effects of GSK598809 are mainly additive and the combination is well tolerated in healthy volunteers.


The effects of TPA023, a GABAA α 2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol.
de Haas SL, Zoethout RW, Van Dyck K, Smet MD, Rosen LB, Murphy MG, Gottesdiener KM, Schoemaker RC, Cohen AF, van Gerven JM.
J Psychopharmacol. 2012; 26: 282-291
The effects of 2 mg TPA023, a GABA(A) α2,3 subtype-selective partial agonist, on essential tremor (ET) were compared to the effects of a stable alcohol level (0.6 g/L) and placebo in nine patients with ET. This study showed that treatment with an α2,3 subunit-selective GABA(A) partial agonist was less effective than a stable level of alcohol in reducing ET symptoms. These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms.

Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study.
Bossong MG, Jager G, van Hell HH, Zuurman L, Jansma JM, Mehta MA, van Gerven JM, Kahn RS, Ramsey NF.
J Cogn Neurosci. 2012; 24: 588-599.
In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of THC inhalation on associative memory-related brain function in 13 healthy volunteers.


The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol.
Zoethout RW, Iannone R, Bloem BR, Palcza J, Murphy G, Chodakewitz J, Buntinx A, Gottesdiener K, Marsilio S, Rosen L, van Dyck K, Louis ED, Cohen AF, Schoemaker RC, Tokita S, Sato N, Koblan KS, Hargreaves RH, Renger JJ, van Gerven JM.
J Psychopharmacol. 2012; 26: 292-302
A steady state of alcohol significantly diminished tremor as assessed by laboratory tremorography, portable tremorography and clinical ratings compared with placebo. A high single MK-0249 dose was not effective in reducing tremor, but caused significant effects on the Leeds Sleep Evaluation Questionnaire and the Choice Reaction Time test.


 

Contact us:
Marieke van den Bosch
Business Development Manager
+31 - 71 - 5246 487
bd@chdr.nl
www.chdr.nl



]]>

CHDR Newsletter March 2012

 

Promasys Newsletter
In February 2012 Promasys launched a new version of a clinical data management and EDC software suite. Furthermore it unveils some features of the future Promasys iPad app.
More information

Bio-Europe Spring Amsterdam, The Netherlands: March 19-21, 2012
The annual international partnering conference, the Bio-Europe Spring will take place in Amsterdam. Together with our partner ABL, CHDR will be present at the event with a stand where our senior consultants will be available for discussions and meetings. In addition, CHDR’s partner organization in the US, CATO Research will join us and together we will be available to present our package of complimentary services. Feel free to visit us at the conference and meet with our consultants in drug development.
Further information on the BIO meeting

Side event Bio-Europe Spring: Life sciences community in Leiden
Following the BIO-Europe, on Thursday 22 March, the Medical Delta & Leiden Bio Science Park the offer the opportunity to get acquainted with the unique life sciences community in Leiden and arrange a visit to the park. The visit will include presentations, field visits to research sites or companies as well as ample networking opportunities. All side visits include transportation from Amsterdam to the side event location and back.
Read more

Side event Bio-Europe Spring: Alzheimer Center
Life Sciences Center Amsterdam is proudly hosting a lightning session entitled ‘Drug Development, Imaging, and Clinical Trials in Alzheimer Disease’, chaired by Dr. Philip Scheltens, Director of the Alzheimer Center at Amsterdam’s VU University Medical Center (VUmc).
Read more


Trials & Techniques

Induction of psychomimetic symptoms with ketamine
In addition to the THC-challenge model that we are developing for psychosis (Liem-Moolenaar et al. 2010, Kleinloog et al. submitted), we performed a trial where S(+)-ketamine was used to induce psychomimetic symptoms as a potential model for psychosis and antipsychotic drug action. Different target concentrations were tested and we found that ketamine can induce a robust, dose-dependent increase on different subscales of the Positive and Negative Syndrome Scale (PANSS) and different tests of the NeuroCart (e.g. smooth pursuit eye movements, adaptive tracking). Although many (side-)effects of ketamine were observed, these were mostly mild and dose-related.
Daniël Kleinloog

Population for Drug Abuse Liability studies
CHDR has performed many studies where healthy volunteers who had to be mild cannabis users were recruited. The subjects in these studies were compared to subjects who participated in other studies, to assess their suitability as a population for drug abuse liability studies. Mild cannabis users were found to be more flexible and open to new experiences than other healthy volunteers. They are also somewhat less cooperative and adherent to social standards, which was associated with a mildly reduced compliance to study procedures. Our experience with recruiting mild cannabis users, the different personality traits and a compliance to study procedures that is expected to be improved compared to a population of polydrug abusers (current standard drug abuse liability studies) makes a strong argument for the use of mild cannabis users in drug abuse liability studies.
Daniël Kleinloog

Posters, Presentations & Publications

PhD-Thesis: Human pharmacology of current and new treatments for schizophrenia
At the 8th of March Marieke Liem-Moolenaar successfully defended her PhD thesis "Human pharmacology of current and new treatments for schizophrenia".
Together, the studies described in this thesis give an impression of the current drug development in schizophrenia, show different ways of studying human pharmacology and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers.
Download Thesis or Recieve a Hardcopy
Marieke Liem-Moolenaar


Involvement of the endocannabinoid system in reward processing in the human brain.
van Hell HH, Jager G, Bossong MG, Brouwer A, Jansma JM, Zuurman L, van Gerven J, Kahn RS, Ramsey NF.
Psychopharmacology (Berl). 2012; 219: 981-990
fMRI has been used to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ(9)-tetrahydrocannabinol (THC) on reward-related brain activity. Results suggest a role for the eCB system in the appreciation of rewards.

Pharmacokinetics and central nervous system effects of the novel dopamine D3 receptor antagonist GSK598809 and intravenous alcohol infusion at pseudo-steady state.
Te Beek ET, Zoethout RW, Bani MS, Andorn A, Iavarone L, Klaassen ES, Fina P, van Gerven JM.
J Psychopharmacol. 2012; 26: 303-314
 In a blinded, randomized, placebo-controlled study, effects of a single oral dose of a novel dopamine D3 receptor antagonist were evaluated in healthy volunteers. Pharmacokinetics, central nervous system (CNS) effects and potential for interaction with alcohol were evaluated, using an alcohol infusion paradigm and CHDR’s NeuroCart CNS test battery. After co-administration with alcohol, effects of GSK598809 are mainly additive and the combination is well tolerated in healthy volunteers.


The effects of TPA023, a GABAA α 2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol.
de Haas SL, Zoethout RW, Van Dyck K, Smet MD, Rosen LB, Murphy MG, Gottesdiener KM, Schoemaker RC, Cohen AF, van Gerven JM.
J Psychopharmacol. 2012; 26: 282-291
The effects of 2 mg TPA023, a GABA(A) α2,3 subtype-selective partial agonist, on essential tremor (ET) were compared to the effects of a stable alcohol level (0.6 g/L) and placebo in nine patients with ET. This study showed that treatment with an α2,3 subunit-selective GABA(A) partial agonist was less effective than a stable level of alcohol in reducing ET symptoms. These results provide no support for a therapeutic role of TPA023 in the suppression of ET symptoms.

Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study.
Bossong MG, Jager G, van Hell HH, Zuurman L, Jansma JM, Mehta MA, van Gerven JM, Kahn RS, Ramsey NF.
J Cogn Neurosci. 2012; 24: 588-599.
In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of THC inhalation on associative memory-related brain function in 13 healthy volunteers.


The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol.
Zoethout RW, Iannone R, Bloem BR, Palcza J, Murphy G, Chodakewitz J, Buntinx A, Gottesdiener K, Marsilio S, Rosen L, van Dyck K, Louis ED, Cohen AF, Schoemaker RC, Tokita S, Sato N, Koblan KS, Hargreaves RH, Renger JJ, van Gerven JM.
J Psychopharmacol. 2012; 26: 292-302
A steady state of alcohol significantly diminished tremor as assessed by laboratory tremorography, portable tremorography and clinical ratings compared with placebo. A high single MK-0249 dose was not effective in reducing tremor, but caused significant effects on the Leeds Sleep Evaluation Questionnaire and the Choice Reaction Time test.


 

Contact us:
Marieke van den Bosch
Business Development Manager
+31 - 71 - 5246 487
bd@chdr.nl
www.chdr.nl



]]> 2012-03-30T17:26:52+02:00 PhD-Thesis by Marieke Liem-Moolenaar http://www.chdr.nl/default.asp?id=778&nieuwsid=159

At the 8th of March Marieke Liem-Moolenaar successfully defended her PhD thesis "Human pharmacology of current and new treatments for schizophrenia".

In this thesis the human pharmacology (the interaction between a drug and human) of current and new drugs for schizophrenia is discussed. Schizophrenia is one of the most debilitating psychiatric disorders and affects 1-1.5% of the world population. It usually occurs in young adults and remains present throughout life.

The studies in this thesis together give an impression of the current drug development in schizophrenia, show different ways of studying human pharmacology and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers.

The investigated compounds show that the main pharmacological focus in this area has shifted from psychosis to improvement of individual negative or cognitive symptom complexes, from direct receptor inhibition to indirect receptor modulation, and from single drug strategies to combination therapies, each targeted at different symptoms.

We have tried to create a pharmacological fingerprint of the investigated compounds by making use of an intensive CNS test battery to measure effects in different functional domains of the brain and additional ‘tools’ (i.e. positive controls, dose escalation, PK-PD modeling and pharmacological challenge tests) to improve the reliability of the tests.

This diversity of drug development strategies and range of neurotransmitters in schizophrenia reflects the increasing complexity of neuropharmacological hypotheses in this field. Despite these difficulties, incremental changes in drug characteristics and treatment strategies may well lead to the introduction of new classes or combinations of drugs in the future.

More information to Download Thesis or Recieve a Hardcopy

]]>

At the 8th of March Marieke Liem-Moolenaar successfully defended her PhD thesis "Human pharmacology of current and new treatments for schizophrenia".

In this thesis the human pharmacology (the interaction between a drug and human) of current and new drugs for schizophrenia is discussed. Schizophrenia is one of the most debilitating psychiatric disorders and affects 1-1.5% of the world population. It usually occurs in young adults and remains present throughout life.

The studies in this thesis together give an impression of the current drug development in schizophrenia, show different ways of studying human pharmacology and provide examples how human pharmacology can be applied in an early stage of drug development in healthy volunteers.

The investigated compounds show that the main pharmacological focus in this area has shifted from psychosis to improvement of individual negative or cognitive symptom complexes, from direct receptor inhibition to indirect receptor modulation, and from single drug strategies to combination therapies, each targeted at different symptoms.

We have tried to create a pharmacological fingerprint of the investigated compounds by making use of an intensive CNS test battery to measure effects in different functional domains of the brain and additional ‘tools’ (i.e. positive controls, dose escalation, PK-PD modeling and pharmacological challenge tests) to improve the reliability of the tests.

This diversity of drug development strategies and range of neurotransmitters in schizophrenia reflects the increasing complexity of neuropharmacological hypotheses in this field. Despite these difficulties, incremental changes in drug characteristics and treatment strategies may well lead to the introduction of new classes or combinations of drugs in the future.

More information to Download Thesis or Recieve a Hardcopy

]]> 2012-03-30T17:26:52+02:00 Promasys Newsletter February 2012 http://www.chdr.nl/default.asp?id=778&nieuwsid=152 Dear reader, 

Please Click Here to read the Promasys newsletter of February 2012. It highlights our newest software release, Promasys version 6.2.

It unveils some features of the Promasys iPad app under development. It introduces our new customers and briefly describes our customer support services in Japan.

We hope you will enjoy reading it. Please feel free to share the newsletter with interested colleagues or friends.

 

About PROMASYS

PROMASYS: integrated CDMS and EDC 

Promasys® is an integrated clinical data management and EDC system that brings quality and efficiency to your clinical data capture and data management processes. On top of industry standard data management functionality -which is available to the users without having to do any programming- Promasys offers rich reporting and  work flow support solutions, like automatic distribution of subject recruitment progress reports, automatic generation of bar-coded sample tube labels, work lists, data listings and SAS data sets, etc. 

Some of Promasys' main features include:

  • easy setup of new trials; use templates and recyclable trial design elements
  • paper CRFs, EDC screens, forms and labels are all generated from the clinical database design
  • build edit checks without programming
  • manual queries and system generated batch queries
  • full audit trail compliant with 21 CFR part 11
  • electronic signatures
  • set & forget access control, dynamic access rights management through the Study Life Cycle
]]> Dear reader, 

Please Click Here to read the Promasys newsletter of February 2012. It highlights our newest software release, Promasys version 6.2.

It unveils some features of the Promasys iPad app under development. It introduces our new customers and briefly describes our customer support services in Japan.

We hope you will enjoy reading it. Please feel free to share the newsletter with interested colleagues or friends.

 

About PROMASYS

PROMASYS: integrated CDMS and EDC 

Promasys® is an integrated clinical data management and EDC system that brings quality and efficiency to your clinical data capture and data management processes. On top of industry standard data management functionality -which is available to the users without having to do any programming- Promasys offers rich reporting and  work flow support solutions, like automatic distribution of subject recruitment progress reports, automatic generation of bar-coded sample tube labels, work lists, data listings and SAS data sets, etc. 

Some of Promasys' main features include:

  • easy setup of new trials; use templates and recyclable trial design elements
  • paper CRFs, EDC screens, forms and labels are all generated from the clinical database design
  • build edit checks without programming
  • manual queries and system generated batch queries
  • full audit trail compliant with 21 CFR part 11
  • electronic signatures
  • set & forget access control, dynamic access rights management through the Study Life Cycle
]]> 2012-02-28T17:26:52+02:00 Visit Alzheimer Center http://www.chdr.nl/default.asp?id=778&nieuwsid=151 22 March 2012: 12.00 – 14.00 h, lunch served

Alzheimer Disease presents challenges on many fronts; the complexity of diagnosis, clinical management, and the continuing unfulfilled search for effective therapy signals that we need to adopt new ways of cooperating to make progress. In this spirit, Life Sciences Center Amsterdam is proudly hosting a lightning session entitled ‘Drug Development, Imaging, and Clinical Trials in Alzheimer Disease’, chaired by Dr. Philip Scheltens, Director of the Alzheimer Center at Amsterdam’s VU University Medical Center (VUmc).

We will bring together in one room experts from key elements of drug development and clinical trial value chain within AD, including:

·         VUmc’s first-in-man trials capability in AD therapeutics, in conjunction with CHDR

·         Full integration with Imaging Center VUmc, which offers radionuclide labeling, toxicology and pharmacokinetics, full GMP lab capabilities, PET Tracer development, and combined PET/MRI

·         Intimate linkage with EATRIS (European Advanced Translational Research InfraStructure in Medicine) headquartered at VUmc

·         Blood-brain barrier delivery companies

·         AD compound companies

·         Multiple ongoing Phase I/II/III trials in AD

·         A large and very well characterized patient population of AD, especially early onset AD

·         Extensive AD biology research, coupled with Neuroscience Campus Amsterdam and beyond

 

VUmc is a conveniently located a short distance away not only from BIO-Europe conference hotels but also Schiphol Airport.

Please note – in the interest of maintaining a tight focus for this short duration and intimate event, RSVP’s will be prioritized according to direct contribution to the discussion. For this reason, LSCA may respectfully decline RSVP’s from upstream or downstream service providers.

Please RSVP to bd@chdr.nl

]]> 22 March 2012: 12.00 – 14.00 h, lunch served

Alzheimer Disease presents challenges on many fronts; the complexity of diagnosis, clinical management, and the continuing unfulfilled search for effective therapy signals that we need to adopt new ways of cooperating to make progress. In this spirit, Life Sciences Center Amsterdam is proudly hosting a lightning session entitled ‘Drug Development, Imaging, and Clinical Trials in Alzheimer Disease’, chaired by Dr. Philip Scheltens, Director of the Alzheimer Center at Amsterdam’s VU University Medical Center (VUmc).

We will bring together in one room experts from key elements of drug development and clinical trial value chain within AD, including:

·         VUmc’s first-in-man trials capability in AD therapeutics, in conjunction with CHDR

·         Full integration with Imaging Center VUmc, which offers radionuclide labeling, toxicology and pharmacokinetics, full GMP lab capabilities, PET Tracer development, and combined PET/MRI

·         Intimate linkage with EATRIS (European Advanced Translational Research InfraStructure in Medicine) headquartered at VUmc

·         Blood-brain barrier delivery companies

·         AD compound companies

·         Multiple ongoing Phase I/II/III trials in AD

·         A large and very well characterized patient population of AD, especially early onset AD

·         Extensive AD biology research, coupled with Neuroscience Campus Amsterdam and beyond

 

VUmc is a conveniently located a short distance away not only from BIO-Europe conference hotels but also Schiphol Airport.

Please note – in the interest of maintaining a tight focus for this short duration and intimate event, RSVP’s will be prioritized according to direct contribution to the discussion. For this reason, LSCA may respectfully decline RSVP’s from upstream or downstream service providers.

Please RSVP to bd@chdr.nl

]]> 2012-02-24T17:26:52+02:00 Bio-Europe Spring, 19-21 March 2012, Amsterdam http://www.chdr.nl/default.asp?id=778&nieuwsid=148 Bio-Europe Spring Amsterdam, The Netherlands: March 19-21, 2012 
The annual international partnering conference, the Bio-Europe Spring will take place in Amsterdam. CHDR will be present at the event with a stand where our senior consultants will be available for discussions and meetings. In addition, CHDR’s partner organization in the US, CATO Research will join us and together we will be available to present our package of complimentary services. Feel free to visit us at the conference and meet with our consultants in drug development.
Further information on the BIO meeting

Following the BIO-Europe, on Thursday 22 March, the Medical Delta & Leiden Bio Science Park the offer the opportunity to get acquainted with the unique life sciences community in Leiden and arrange a visit to the park. The visit will include presentations, field visits to research sites or companies as well as ample networking opportunities. All side visits include transportation from Amsterdam to the side event location and back.
Read more

]]> Bio-Europe Spring Amsterdam, The Netherlands: March 19-21, 2012 
The annual international partnering conference, the Bio-Europe Spring will take place in Amsterdam. CHDR will be present at the event with a stand where our senior consultants will be available for discussions and meetings. In addition, CHDR’s partner organization in the US, CATO Research will join us and together we will be available to present our package of complimentary services. Feel free to visit us at the conference and meet with our consultants in drug development.
Further information on the BIO meeting

Following the BIO-Europe, on Thursday 22 March, the Medical Delta & Leiden Bio Science Park the offer the opportunity to get acquainted with the unique life sciences community in Leiden and arrange a visit to the park. The visit will include presentations, field visits to research sites or companies as well as ample networking opportunities. All side visits include transportation from Amsterdam to the side event location and back.
Read more

]]> 2012-01-30T17:26:52+02:00 Bibliometric research performance profile http://www.chdr.nl/default.asp?id=778&nieuwsid=149 Bibliometric research performance profile

Using scientific publication and citation data, a bibliometric research performance analysis has been performed to measure the scientific impact and visibility of CHDR.
The number of scientific publications, P, over the last decade (2001 -2010) shows that CHDR has a substantial scientific oeuvre with an increasing volume since 2004 with a performance above world average.

The overall field normalized impact indication (MNCS, mean normalized citation score) - being the most suitable indicator for the international position of an oeuvre - demonstrates a substantial growth of the scientific impact which has grown to well above the world average of 1.




Contact us:
Marieke van den Bosch
Business Development Manager
+31 - 71 - 5246 487
bd@chdr.nl
www.chdr.nl



]]> Bibliometric research performance profile

Using scientific publication and citation data, a bibliometric research performance analysis has been performed to measure the scientific impact and visibility of CHDR.
The number of scientific publications, P, over the last decade (2001 -2010) shows that CHDR has a substantial scientific oeuvre with an increasing volume since 2004 with a performance above world average.

The overall field normalized impact indication (MNCS, mean normalized citation score) - being the most suitable indicator for the international position of an oeuvre - demonstrates a substantial growth of the scientific impact which has grown to well above the world average of 1.




Contact us:
Marieke van den Bosch
Business Development Manager
+31 - 71 - 5246 487
bd@chdr.nl
www.chdr.nl



]]> 2012-01-30T17:26:52+02:00