Clinical trial NCT05624528: A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder
Official title: A Double-Blind, Randomized, Placebo-Controlled Study of Tolcapone for OCD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
OCD
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2022-11-22
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Yale Brown Obsessive Compulsive Scale (YBOCS)
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: CANTAB Cognitive Testing
timeFrame: Baseline to Week 8
measure: Val-158-Met polymorphism
timeFrame: Baseline to Week 8
measure: Quality of Life Inventory
timeFrame: Baseline to Week 8
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: Baseline to Week 8
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
Study officials:
affiliation: University of Chicago
name: Jon E Grant, MD, JD, MPH
role: PRINCIPAL_INVESTIGATOR
References: