Obsessive-Compulsive DisorderPhase 2NCT05624528
A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder
A Phase 2 study testing Tolcapone in people with Obsessive-Compulsive Disorder and OCD, run by University of Chicago at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obsessive-Compulsive Disorder, OCD
- What is being tested?
- Tolcapone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2023to 1 Jun 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Medical Center
Chicago, Illinois, 60637
About this study
Official title: 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.
Read the 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.
- Conditions
- Obsessive-Compulsive Disorder, OCD
- Being tested
- Tolcapone, Placebo
- Medical subject headings
- Obsessive-Compulsive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
catechol-O-methyl transferase inhibitor
PlaceboDrug
Pill that contains no medicine
| Study group | Role | What they receive |
|---|---|---|
| Tolcapone | Experimental | 100mg of tolcapone twice daily for two weeks, then 200mg tolcapone twice daily for the remaining six weeks. Receives: Drug: Tolcapone |
| Placebo | Placebo comparator | 100mg of placebo twice daily for two weeks, then 200mg of placebo twice daily for the remaining six weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 8
Secondary outcomes (4)
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.
Measured: 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.
Measured: Baseline
Change in Quality of Life Inventory (QOLI) Standardized T-Scores
The Quality of Life Inventory (QOLI) is a self-report assessment measuring patient perceived quality of life. QOLI T-scores will be assessed at baseline and visit 5 (8 weeks). The change in standardized T-scores from baseline to visit 5 at week 8 will be reported. 50 indicates the population mean of T-score values with a standard deviation of 10. QOLI T-scores range from 0-77. Higher T-scores (above 60) indicate high or above-average quality of life, whereas lower T-scores (below 40) indicate a lower or less-than-average quality of life
Measured: Baseline to Week 8
Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
The MADRS is a 10-item clinical rated scale measuring depression severity. The change from baseline to Visit 5 (8 weeks) will be reported. Higher total scores (ranging from 0-60) indicate higher severity levels of depression, while a score of 0 would indicate no depressive symptoms.
Measured: Baseline to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start22 Jun 2023
- Primary completion1 Jun 2026
- Study completion1 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Obsessive-Compulsive DisorderStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jon E Grant, MD, JD, MPH, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624528
- Sponsor's protocol ID
- IRB22-1729
- Status last verified
- Sep 2026
- First submitted
- 14 Nov 2022
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No