Clincosm LogoSign in Get a demo

Tolcapone in Obsessive Compulsive Disorder

Sponsor
University of Chicago (Other)
Overall Status
Completed
CT.gov ID
NCT03348930
Collaborator
(none)
20
Enrollment
1
Location
2
Arms
32.9
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The proposed study will consist of a 5-week double-blind cross-over study trial of tolcapone in 20 people (ages 18-65). The study will be divided into an initial 2 week phase and a second 2 week phase, with one of the 2 week phases consisting of active treatment with tolcapone, and the other 2 week phase consisting of inactive placebo treatment. There will be a one-week wash-out phase between the 2-week treatment phases. Participants will be randomized to receive either tolcapone or placebo during the first 2 week phase on a 1:1 basis. This blinding will be maintained by the IDS pharmacy at the University of Chicago.

Condition or Disease Intervention/Treatment Phase
  • Drug: Tolcapone 200 MG
 Phase 2/Phase 3

Detailed Description

The goal of the proposed study is to evaluate the efficacy and safety of tolcapone in adults with obsessive compulsive disorder (OCD). The hypothesis to be tested is that tolcapone will be more effective and well tolerated in adults with OCD compared to placebo. The proposed study will provide needed data on the treatment of a disabling disorder where current treatments are often ineffective.

The primary aim of this application is to conduct a randomized placebo-controlled pharmacotherapy trial using tolcapone in 20 participants with OCD. The study will consist of two phases: a 2 week active treatment phase with tolcapone, a one-week wash-out phase, and a 2 week placebo phase. The subjects will be randomized to either receive tolcapone or placebo treatment in the first 2 weeks, and the other during the remaining 2 week phase.

This will be one of few studies assessing the use of pharmacotherapy for the treatment of OCD in adults. Assessing the efficacy and safety of tolcapone will help inform clinicians about additional treatment options for adults suffering from this disorder.

Study Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Tolcapone Treatment of Obsessive Compulsive Disorder: A Double-Blind, Placebo-Controlled, Cross-Over Pilot Study
Actual Study Start Date :
Mar 20, 2018
Actual Primary Completion Date :
Dec 14, 2020
Actual Study Completion Date :
Dec 14, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tolcapone

Each subject will have a 4 week treatment phase with Tolcapone

Drug: Tolcapone 200 MG
All eligible study subjects will go through a 2-week treatment phase during which they will begin tolcapone at 100mg twice a day.
Other Names:
  • No other names

    		•
    Placebo Comparator: Placebo

    4 week placebo phase before or after Tolcapone phase depending on randomization.

    Drug: Tolcapone 200 MG
    All eligible study subjects will go through a 2-week treatment phase during which they will begin tolcapone at 100mg twice a day.
    Other Names:
  • No other names

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Yale Brown Obsessive Compulsive Scale (Y-BOCS) [2 weeks (start of study to washout period OR two weeks following washout period)]

      The entire study for the subject will last 5 weeks. Every 2 weeks and after the one week washout period the subject will take the YBOCS. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses severity of OCD symptoms. The YBOCS scale ranges from 0 to 40, with 0 being no symptoms and 40 being severe.

    Secondary Outcome Measures

    1. Clinical Global Impression- Severity and Improvement (CGI) [2 weeks (start of study to washout period OR two weeks following washout period)]

      The entire study for the subject will last 5 weeks. Every two weeks and after the one week washout period the subject will complete the CGI. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses overall disorder severity on a scale from 1 to 7 with 1 being "not at all" and 7 being "among the most severe cases"

    2. Sheehan Disability Scale (SDS) [2 weeks (start of study to washout period OR two weeks following washout period)]

      The entire study for the subject will last 5 weeks. Every two weeks and after the one week washout period the subject will complete the SDS. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses the level of disability from obsessive compulsive disorder (or target disorder). The SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. Work/school scores range from 0 to 10, Social life scores range from 0 to 10, Family life/home responsibilities scores range from 0 to 10). Total scores are calculated by adding the scores for work/school, social life, and family life. Total scores range from a minimum of 0 to a maximum of 30 (0 unimpaired, 30 highly impaired).

    3. Hamilton Anxiety Rating Scale (HAM-A) [2 weeks (start of study to washout period OR two weeks following washout period)]

      Every study visit, the subject will complete the HAM-A. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses level of anxiety. Higher scores indicate higher levels of anxiety, with 0 being no symptoms of anxiety and 30 being severe anxiety.

    4. Hamilton Depression Rating Scale (HAM-D) [2 weeks (start of study to washout period OR two weeks following washout period)]

      The entire study for the subject will last 5 weeks. The HAM-D will be administered at every study visit. The change in scores from baseline to after the end of the 2-week active treatment period will be assessed and the change in scores from baseline to the end of the 2-week placebo period. The scale itself assesses level of depression. The minimum score is 0 and indicates no depressive symptoms, while the highest possible score is 50. Higher total scores indicate high levels of depression. Higher scores indicate a worse outcome. Higher total scored (14-50) indicate higher levels of depression, while a score between 0-7 is considered normal.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Males and females age 18-65;

    2. Diagnosis of current OCD based on DSM-5 criteria and confirmed using the clinician-administered Structured Clinical Interview for DSM-5 (SCID);

    3. Able and willing to provide written consent for participation.

    Exclusion Criteria:

    1. Unstable medical illness, including liver disease, as determined by the investigator;

    2. History of seizures;

    3. Clinically significant suicidality (defined by the Columbia Suicide Severity Rating Scale);

    4. Baseline score of ≥17 on the Hamilton Depression Rating Scale (17-item HDRS);

    5. Lifetime history of bipolar disorder type I or II, schizophrenia, autism, any psychotic disorder, or any substance use disorder;

    6. Initiation of psychotherapy or behavior therapy within 3 months prior to study baseline;

    7. Previous treatment with tolcapone;

    8. Any history of psychiatric hospitalization in the past year;

    9. Currently pregnant (confirmed by urine pregnancy test)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Chicago Chicago Illinois United States 60637

    Sponsors and Collaborators

    • University of Chicago

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    University of Chicago
    ClinicalTrials.gov Identifier:
    NCT03348930
    Other Study ID Numbers:
    • 17-1379
    First Posted:
    Nov 21, 2017
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Compulsive Personality Disorder
    Obsessive-Compulsive Disorder
    Tolcapone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Tolcapone, Then Placebo Placebo, Then Tolcapone
    Arm/Group Description Each subject will have a 2 week active treatment phase first with Tolcapone (100mg, twice a day), followed by a one-week washout period, followed by a 2 week treatment phase with a Tolcapone-matched placebo tablet. Each subject will have a 2 week active treatment phase first with a Tolcapone-matched placebo, followed by a one-week washout period, followed by a 2 week active treatment phase with Tolcapone (100mg, twice a day).
    Period Title: First Intervention (2 Weeks)
    STARTED 10 10
    COMPLETED 10 10
    NOT COMPLETED 0 0
    Period Title: First Intervention (2 Weeks)
    STARTED 10 10
    COMPLETED 9 9
    NOT COMPLETED 1 1
    Period Title: First Intervention (2 Weeks)
    STARTED 9 9
    COMPLETED 9 9
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Tolcapone/Placebo
    Arm/Group Description Each subject will have a 4 week treatment phase with Tolcapone and a 4 week placebo phase before or after Tolcapone phase depending on randomization. Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase during which they will begin tolcapone at 100mg twice a day.
    Overall Participants 20
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    36.9
    (12.73)
    Sex: Female, Male (Count of Participants)
    Female
    8
    40%
    Male
    12
    60%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    12
    60%
    African American
    4
    20%
    Latino/Hispanic
    1
    5%
    Other
    2
    10%
    Not Reported
    1
    5%
    Region of Enrollment (participants) [Number]
    United States
    20
    100%
    Any psychiatric comorbidity (Count of Participants)
    Yes
    9
    45%
    No
    11
    55%

    Outcome Measures

    1. Primary Outcome
    Title Yale Brown Obsessive Compulsive Scale (Y-BOCS)
    Description The entire study for the subject will last 5 weeks. Every 2 weeks and after the one week washout period the subject will take the YBOCS. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses severity of OCD symptoms. The YBOCS scale ranges from 0 to 40, with 0 being no symptoms and 40 being severe.
    Time Frame 2 weeks (start of study to washout period OR two weeks following washout period)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase (either during the first two weeks or last two weeks of the study) during which they will begin tolcapone at 100mg twice a day. All eligible study subjects will go through a 2-week phase (either during the first two weeks or last two weeks of the study) during which they will begin the tolcapone-matched placebo twice a day.
    Measure Participants 19 19
    Mean (Standard Deviation) [mean change in YBOCS score]
    -4.24
    (6.20)
    -1.10
    (4.71)
    2. Secondary Outcome
    Title Clinical Global Impression- Severity and Improvement (CGI)
    Description The entire study for the subject will last 5 weeks. Every two weeks and after the one week washout period the subject will complete the CGI. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses overall disorder severity on a scale from 1 to 7 with 1 being "not at all" and 7 being "among the most severe cases"
    Time Frame 2 weeks (start of study to washout period OR two weeks following washout period)

    Outcome Measure Data

    Analysis Population Description
    Participants who fully completed Visits 2 and 4.
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase (either during the first two weeks or last two weeks of the study) during which they will begin tolcapone at 100mg twice a day. All eligible study subjects will go through a 2-week phase (either during the first two weeks or last two weeks of the study) during which they will begin the tolcapone-matched placebo twice a day.
    Measure Participants 17 19
    Mean (Standard Deviation) [score on a scale]
    3.78
    (1.43)
    3.5
    (0.90)
    3. Secondary Outcome
    Title Sheehan Disability Scale (SDS)
    Description The entire study for the subject will last 5 weeks. Every two weeks and after the one week washout period the subject will complete the SDS. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses the level of disability from obsessive compulsive disorder (or target disorder). The SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. Work/school scores range from 0 to 10, Social life scores range from 0 to 10, Family life/home responsibilities scores range from 0 to 10). Total scores are calculated by adding the scores for work/school, social life, and family life. Total scores range from a minimum of 0 to a maximum of 30 (0 unimpaired, 30 highly impaired).
    Time Frame 2 weeks (start of study to washout period OR two weeks following washout period)

    Outcome Measure Data

    Analysis Population Description
    Subjects who completed all five weeks of the study except for one subjects who's SDS data was missing at all time points (no data to carry forward).
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase (either during the first two weeks or last two weeks of the study) during which they will begin tolcapone at 100mg twice a day. All eligible study subjects will go through a 2-week phase (either during the first two weeks or last two weeks of the study) during which they will begin the tolcapone-matched placebo twice a day.
    Measure Participants 18 18
    Mean (Standard Deviation) [mean change in SDS score]
    -2.68
    (4.41)
    -1.97
    (6.62)
    4. Secondary Outcome
    Title Hamilton Anxiety Rating Scale (HAM-A)
    Description Every study visit, the subject will complete the HAM-A. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses level of anxiety. Higher scores indicate higher levels of anxiety, with 0 being no symptoms of anxiety and 30 being severe anxiety.
    Time Frame 2 weeks (start of study to washout period OR two weeks following washout period)

    Outcome Measure Data

    Analysis Population Description
    Adults with OCD who completed the study.
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase (either during the first two weeks or last two weeks of the study) during which they will begin tolcapone at 100mg twice a day. All eligible study subjects will go through a 2-week phase (either during the first two weeks or last two weeks of the study) during which they will begin the tolcapone-matched placebo twice a day.
    Measure Participants 19 19
    Mean (Standard Deviation) [mean change in HAM-A score]
    -1.90
    (4.39)
    -1.60
    (4.07)
    5. Secondary Outcome
    Title Hamilton Depression Rating Scale (HAM-D)
    Description The entire study for the subject will last 5 weeks. The HAM-D will be administered at every study visit. The change in scores from baseline to after the end of the 2-week active treatment period will be assessed and the change in scores from baseline to the end of the 2-week placebo period. The scale itself assesses level of depression. The minimum score is 0 and indicates no depressive symptoms, while the highest possible score is 50. Higher total scores indicate high levels of depression. Higher scores indicate a worse outcome. Higher total scored (14-50) indicate higher levels of depression, while a score between 0-7 is considered normal.
    Time Frame 2 weeks (start of study to washout period OR two weeks following washout period)

    Outcome Measure Data

    Analysis Population Description
    Adults with OCD who completed the 5-week study.
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Tolcapone 200 MG: All eligible study subjects will go through a 2-week treatment phase (either during the first two weeks or last two weeks of the study) during which they will begin tolcapone at 100mg twice a day. All eligible study subjects will go through a 2-week phase (either during the first two weeks or last two weeks of the study) during which they will begin the tolcapone-matched placebo twice a day.
    Measure Participants 19 19
    Mean (Standard Deviation) [mean change in HAM-D score]
    -1.65
    (3.67)
    -2.00
    (4.42)

    Adverse Events

    Time Frame Adverse event data were collected through study completion, as necessary over the period of 5 week (the length of the trial).
    Adverse Event Reporting Description
    Arm/Group Title Tolcapone Placebo
    Arm/Group Description Subjects received 100mg of tolcapone twice a day for two weeks either starting after the baseline visit, or starting after the 1-week washout period. Subjects received tolcapone-matched placebo twice a day for two weeks either starting after the baseline visit, or starting after the 1-week washout period.
    All Cause Mortality
    Tolcapone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/20 (0%) 0/20 (0%)
    Serious Adverse Events
    Tolcapone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/20 (0%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    Tolcapone Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/20 (15%) 5/20 (25%)
    Gastrointestinal disorders
    Increased frequency in bowel movements 1/20 (5%) 0/20 (0%)
    Blood in stool 1/20 (5%) 0/20 (0%)
    Less frequent bowel movements 0/20 (0%) 1/20 (5%)
    General disorders
    Mild Headache 1/20 (5%) 0/20 (0%)
    Fatigue 0/20 (0%) 1/20 (5%)
    Muscle aching 0/20 (0%) 1/20 (5%)
    Joint stiffness 0/20 (0%) 1/20 (5%)
    Sleep problems 0/20 (0%) 1/20 (5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Jon Grant
    Organization University of Chicago
    Phone 7738341325
    Email jgrant4@bsd.uchicago.edu
    Responsible Party:
    University of Chicago
    ClinicalTrials.gov Identifier:
    NCT03348930
    Other Study ID Numbers:
    • 17-1379
    First Posted:
    Nov 21, 2017
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Mar 1, 2022