A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder

University of Chicago49 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Obsessive-Compulsive Disorder OCD

Interventions

TolcaponeDRUG

catechol-O-methyl transferase inhibitor

PlaceboDRUG

Pill that contains no medicine

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Chicago Medical Center

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Total Score

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a clinician-administered measure of OCD illness severity (total scores range from 0-40). Higher scores indicate more severe symptoms. The Y-BOCS will be administered three times throughout the study, but only change from baseline to Visit 5 (8 weeks) will be reported.

Time frame: Baseline to Week 8

Secondary Outcomes

Change in Cambridge Neuropsychological Test Automated Battery (CANTAB) Scores

The Cambridge Neuropsychological Test Automated Battery (CANTAB) includes neuropsychological tasks measuring cognition. Changes in scores from baseline to Visit 5 will be reported. Each task is scored either by Z-scores or percentile ranks compared to the normative group, where a Z-score of 0 represents the population mean. For all scales, standard deviations above the mean Z-score represent better outcomes. Descriptions of each task are as follows Cambridge Gambling Task (CGT): Measures decision-making and risk-taking. Intra-Extra Dimensional Set Shift (IED) Task: Measures rule acquisition and reversal learning. One Touch Stockings of Cambridge (OTS) Task: Measures spatial planning and working memory. Spatial Working Memory (SWM) Task: Measures ability to remember spatial information and to use working memory. Rapid Visual Processing (RVP) Task: Measures continuous performance and sustained visual attention.

Time frame: Baseline to Week 8

Number of Participants With Different Variants of Val-158-Met SNP

Evaluating whether the single nucleotide polymorphism (SNP) Val-158-Met polymorphism significantly relates to changes in symptoms and cognition observed with tolcapone. We hypothesize that the val/val catechol-O-methyltransferase (COMT) variant will be associated with significantly higher tolcapone-related improvements in cognition and symptoms, since this is linked to lower cortical dopamine function.

Time frame: Baseline

Change in Quality of Life Inventory (QOLI) Standardized T-Scores

Data from ClinicalTrials.gov

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