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

Primary Purpose

Obsessive-Compulsive Disorder

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Pramipexole, Amisulpride
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obsessive-Compulsive Disorder focused on measuring Dopamine, OCD, MRI, stimulant users

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational Site

Outcomes

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.

Secondary Outcome Measures

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

Full Information

First Posted
May 8, 2007
Last Updated
September 11, 2014
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00471588
Brief Title
Characterize The Modulatory Effects Of Dopamine D2/D3 Receptor Agonist And Antagonist Drugs On Compulsive Behaviors
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 Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-Compulsive Disorder
Keywords
Dopamine, OCD, MRI, stimulant users

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pramipexole, Amisulpride
Other Intervention Name(s)
Pramipexole, Amisulpride
Intervention Description
Study Drug
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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.
Title
Measure of brain functional activation at rest.
Time Frame
up to week 3
Title
Measure of behavioural performance
Time Frame
up to week 3
Title
Measure of peripheral blood for gene expression and proteomic changes.
Time Frame
up to week 3
Title
Genetic variation in selected genes
Time Frame
up to week 3
Title
Clinical measures (SSRS, SSR, BL-VAS, BDI-II)
Time Frame
up to week 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom

12. IPD Sharing Statement

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

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