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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00471588

Collaborator

(none)

Enrollment

Location

Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder	Drug: Pramipexole, Amisulpride	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, 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

Study Start Date :

Aug 1, 2006

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Outcome Measures

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. [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. [on Week 1 only.]
Measure of brain functional activation at rest. [up to week 3]
Measure of behavioural performance [up to week 3]
Measure of peripheral blood for gene expression and proteomic changes. [up to week 3]
Genetic variation in selected genes [up to week 3]
Clinical measures (SSRS, SSR, BL-VAS, BDI-II) [up to week 3]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.