A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Obsessive-Compulsive Disorder; OCD
• Intervention / Treatment: Drug: Placebo; Drug: Tolcapone

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Madison P Collins, BA; Phone Number: 773-834-3778; Email: [email protected]

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 64 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tolcapone; 100mg of tolcapone twice daily for two weeks, then 200mg tolcapone twice daily for the remaining six weeks.	Drug: Tolcapone; catechol-O-methyl transferase inhibitor; Other Names: Tasmar
Placebo Comparator: Placebo; 100mg of placebo twice daily for two weeks, then 200mg of placebo twice daily for the remaining six weeks.	Drug: Placebo; Pill that contains no medicine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale Brown Obsessive Compulsive Scale (YBOCS)	A measure of OCD illness severity	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CANTAB Cognitive Testing	Neuropsychological tasks that measure cognition	Baseline to Week 8
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
Quality of Life Inventory	A self-report measure assessing perceived quality of life.	Baseline to Week 8
Montgomery-Asberg Depression Rating Scale	A 10-item clinical rated scale measuring depression severity.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Jon E Grant, MD, JD, MPH, University of Chicago

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Tolcapone
• Other Study ID Numbers: IRB22-1729

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No