A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder

Obsessive-Compulsive Disorder Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled Study of Tolcapone for OCD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05624528
• Other study ID #: IRB22-1729
• Status: Recruiting
• Phase: Phase 2
• Start date: June 22, 2023
• Est. completion date: July 2025

Study information

• Verified date: July 2023
• Source: University of Chicago
• Contact: Madison P Collins, BA
• Phone: 773-834-3778
• Email: mcollins4[@]bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary aim of the present study is to examine the efficacy and safety of tolcapone in adults with moderate to severe OCD.

Description:

Based on the mechanism of action and our previous pilot data, the primary aim of the present study is to examine the efficacy and safety of 8-week treatment with tolcapone vs. placebo in adults with moderate to severe OCD, as indicated by a score of at least 21 on the Yale Brown Obsessive Compulsive Scale (YBOCS), a scale of illness severity, at the baseline visit. We hypothesize that tolcapone will significantly improve symptoms of OCD compared to placebo.

A secondary aim of the proposed study is to examine the cognitive effects of tolcapone in OCD, by conducting objective neuropsychological tasks pre- and post-pharmacological trial. The rationale for this approach is that: dopamine plays a key role in cognition; cognitive effects of tolcapone are likely to be relevant in explaining symptomatic effects; and cognitive dysfunction constitutes an important treatment target in OCD that is not generally ameliorated by current first-line interventions. We hypothesize that any symptomatic benefit with tolcapone would also be associated with improvement in executive functions including cognitive flexibility.

Another secondary aim of the proposed study is to evaluate whether the single nucleotide polymorphism (SNP) Val-158-Met polymorphism significantly relates to changes in symptoms and cognition observed with tolcapone. Prior data indicate cognitive effects of tolcapone are affected by this SNP. We hypothesize that the val/val COMT variant will be associated with significantly higher tolcapone-related improvements in cognition and symptoms, since this is linked to lower cortical dopamine function.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: July 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Men and women age 18-65 years

2. Primary diagnosis of OCD

3. YBOCS score of at least 21 at baseline (moderate or higher severity)

4. Ability to understand and sign the consent form

Exclusion Criteria:

1. Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination

2. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential

3. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)

4. History of psychosis or bipolar disorder based on DSM-5 criteria

5. Alcohol/substance use disorder and/or illegal substance use based on urine toxicology

6. Initiation of psychological interventions within 3 months of screening (those who are continuing with CBT will be included)

7. Use of any new psychotropic medication within 3 months of study entry (stable doses of psychotropics will be allowed)

8. Major cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent

9. Abnormal liver function tests at baseline

10. MADRS >30 at baseline

Related Conditions & MeSH terms

• Obsessive-Compulsive Disorder
• OCD

Intervention

Drug:
• Tolcapone
catechol-O-methyl transferase inhibitor
• Placebo
Pill that contains no medicine

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Yale Brown Obsessive Compulsive Scale (YBOCS)	A measure of OCD illness severity	Baseline to Week 8
Secondary	CANTAB Cognitive Testing	Neuropsychological tasks that measure cognition	Baseline to Week 8
Secondary	Val-158-Met polymorphism	Evaluating whether the single nucleotide polymorphism (SNP) Val-158-Met polymorphism significantly relates to changes in symptoms and cognition observed with tolcapone.	Baseline to Week 8
Secondary	Quality of Life Inventory	A self-report measure assessing perceived quality of life.	Baseline to Week 8
Secondary	Montgomery-Asberg Depression Rating Scale	A 10-item clinical rated scale measuring depression severity.	Baseline to Week 8