Characterize The Modulatory Effects Of Dopamine D2/D3 Receptor Agonist And Antagonist Drugs On Compulsive Behaviors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00471588
First received: May 8, 2007
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

3 groups of subjects (healthy controls, OCD subjects and stimulant-dependent subjects) will receive pramipexole (1.5 mg, single dose), amisulpride (400 mg, single dose) or placebo in a cross-over, double-blind, placebo-controlled design.

Effects of compulsive behaviour will be assessed using fMRI and cognitive testing.

Assess biomarkers including cardiovascular responses and plasma levels. All groups studied on 3 separate occasions following screening, with at least a week intervening between consecutive assessments. The procedures to be adopted for study assessment will be identical on each occasion.


Condition Intervention Phase
Obsessive-Compulsive Disorder
Drug: Pramipexole, Amisulpride
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Dopamine D2/D3 Receptor Agonist and Antagonist Drug Effects on Fronto-striatal Systems Related to Compulsive Behaviour in Healthy Volunteers and Patients With Addictive and Compulsive Disorders

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Investigate that drug addicts or OCD patients will show similar abnormalities of compulsive behaviour and functional activation of ventral fronto-striatal systems. MRI scans will occur on Wk 1, 2 and 3. Neuropsychological testing Wk 1, 2 and 3. [ Time Frame: on Wk 1, 2 and 3 ]

Secondary Outcome Measures:
  • Test the prediction that a dopamine D2/D3 agonist drug (pramipexole)by PK levels. PK sample taken on Week 1 only. [ Time Frame: on Week 1 only. ]
  • Measure of brain functional activation at rest. [ Time Frame: up to week 3 ]
  • Measure of behavioural performance [ Time Frame: up to week 3 ]
  • Measure of peripheral blood for gene expression and proteomic changes. [ Time Frame: up to week 3 ]
  • Genetic variation in selected genes [ Time Frame: up to week 3 ]
  • Clinical measures (SSRS, SSR, BL-VAS, BDI-II) [ Time Frame: up to week 3 ]

Enrollment: 52
Study Start Date: August 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pramipexole, Amisulpride
    Study Drug
    Other Names:
    • Pramipexole
    • Amisulpride
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female, between 18 - 55 years of age; the groups will be matched for either handedness.
  • Participants must have the ability to comprehend the key components of the consent form and provide informed consent.
  • Participants must lead and write (in English) at a level sufficient to complete study related assessments.
  • Assessment by a psychiatrist or psychologist, which includes a face-to-face evaluation of the individual using the DSM-VI diagnosis.
  • No history of neurological disorder, head/brain injury, hepatitis, or visual impairment.
  • No MRI contra-indications (metal in body, claustrophobia) and able to provide blood samples (venous accessibility, especially relevant for drug users).
  • Patients with obsessive-compulsive disorder will have a minimum 2-year history of compulsive behaviours satisfying DSM-IV-TR criteria for OCD.
  • Participants with chronic stimulant use will have a minimum 2-year history of dependence on class A stimulants, with age of drug abuse onset before 20 years, and will satisfy DSM-IV-TR criteria for dependence on stimulant drugs.
  • Control volunteers have to be in good mental and physical health.

Exclusion Criteria:

  • A personal history of psychiatric or neurological disorders, as defined by the DSMIV (except OCD in patients with OCD and substance dependence in drug users)
  • A history or presence of alcohol / substance abuse or dependence (other than nicotine), as defined by the DSM-IV-TR (except drug dependence group).
  • A BDI-II total score greater than 14 will lead to exclusion from the study.
  • Treatment with methadone or buprenorphine may interfere with the experimental tasks, and therefore, will lead to exclusion from the study.
  • Participants who have any laboratory abnormality that in the investigator's judgement is considered to be clinically significant and could potentially affect subject safety or study outcome.

    • History of clinically significant or current renal dysfunction.
    • Clinically significant abnormalities in hematology, blood chemistry, MRI, urinalysis or physical examination not resolved by baseline visit.
    • Impaired liver function at baseline or history of liver dysfunction.
    • Female participant is pregnant or currently breastfeeding.
  • Any serious medical disorder or condition that would in the Investigator's opinion, preclude the administration of study medication and or a history of clinically significant hepatic, cardiac, renal, neurologic, cerebrovascular, metabolic or pulmonary disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00471588

Locations
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00471588     History of Changes
Other Study ID Numbers: TMT106512
Study First Received: May 8, 2007
Last Updated: September 11, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Dopamine
OCD
MRI
stimulant users

Additional relevant MeSH terms:
Compulsive Behavior
Compulsive Personality Disorder
Disease
Obsessive-Compulsive Disorder
Anxiety Disorders
Impulsive Behavior
Mental Disorders
Pathologic Processes
Personality Disorders
Dopamine
Dopamine Agents
Pramipexole
Sultopride
Anti-Dyskinesia Agents
Antioxidants
Antiparkinson Agents
Antipsychotic Agents
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agonists
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 20, 2014