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

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

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.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: Pramipexole, Amisulpride

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: May 8, 2007
• First Submitted That Met QC Criteria: May 8, 2007
• First Posted (Estimate): May 10, 2007

Study Record Updates

• Last Update Posted (Estimate): September 15, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: MRI; OCD; Dopamine; stimulant users
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Impulsive Behavior; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Compulsive Behavior; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Dopamine Antagonists; Antidepressive Agents, Second-Generation; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Amisulpride; Pramipexole
• Other Study ID Numbers: TMT106512