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

Obsessive-Compulsive Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00471588
• Other study ID #: TMT106512
• Status: Completed
• Phase: Phase 1
• First received: May 8, 2007
• Last updated: September 11, 2014
• Start date: August 2006
• Est. completion date: December 2007

Study information

• Verified date: September 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

Intervention

Drug:
• Pramipexole, Amisulpride
Study Drug

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Cambridge	Cambridgeshire

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	Measure of brain functional activation at rest.		up to week 3
Secondary	Measure of behavioural performance		up to week 3
Secondary	Measure of peripheral blood for gene expression and proteomic changes.		up to week 3
Secondary	Genetic variation in selected genes		up to week 3
Secondary	Clinical measures (SSRS, SSR, BL-VAS, BDI-II)		up to week 3