A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Obsessive-Compulsive Disorder, OCD

Intervention / Treatment
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* Drug: Tolcapone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age 18-65 years Primary diagnosis of OCD YBOCS score of at least 21 at baseline (moderate or higher severity) Ability to understand and sign the consent form Exclusion Criteria: Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination Current pregnancy or lactation, or inadequate contraception in women of childbearing potential Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs) History of psychosis or bipolar disorder based on DSM-5 criteria Alcohol/substance use disorder and/or illegal substance use based on urine toxicology Initiation of psychological interventions within 3 months of screening (those who are continuing with CBT will be included) Use of any new psychotropic medication within 3 months of study entry (stable doses of psychotropics will be allowed) Major cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent Abnormal liver function tests at baseline MADRS >30 at baseline

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |