Obsessive-Compulsive Disorder
Conditions
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.
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.
Interventions
DRUGTolcapone 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.
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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). |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tolcapone/Placebo 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. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (1 Week) | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Tolcapone/Placebo |
|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 12.73 |
| Any psychiatric comorbidity No | 11 Participants |
| Any psychiatric comorbidity Yes | 9 Participants |
| Race/Ethnicity, Customized African American | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 12 Participants |
| Race/Ethnicity, Customized Latino/Hispanic | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 3 / 20 | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Yale Brown Obsessive Compulsive Scale (Y-BOCS)
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)
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Yale Brown Obsessive Compulsive Scale (Y-BOCS) | -4.24 mean change in YBOCS score | Standard Deviation 6.2 |
| Placebo | Yale Brown Obsessive Compulsive Scale (Y-BOCS) | -1.10 mean change in YBOCS score | Standard Deviation 4.71 |
Secondary
Clinical Global Impression- Severity and Improvement (CGI)
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)
Population: Participants who fully completed Visits 2 and 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Clinical Global Impression- Severity and Improvement (CGI) | 3.78 score on a scale | Standard Deviation 1.43 |
| Placebo | Clinical Global Impression- Severity and Improvement (CGI) | 3.5 score on a scale | Standard Deviation 0.9 |
Secondary
Hamilton Anxiety Rating Scale (HAM-A)
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)
Population: Adults with OCD who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Hamilton Anxiety Rating Scale (HAM-A) | -1.90 mean change in HAM-A score | Standard Deviation 4.39 |
| Placebo | Hamilton Anxiety Rating Scale (HAM-A) | -1.60 mean change in HAM-A score | Standard Deviation 4.07 |
Secondary
Hamilton Depression Rating Scale (HAM-D)
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)
Population: Adults with OCD who completed the 5-week study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Hamilton Depression Rating Scale (HAM-D) | -1.65 mean change in HAM-D score | Standard Deviation 3.67 |
| Placebo | Hamilton Depression Rating Scale (HAM-D) | -2.00 mean change in HAM-D score | Standard Deviation 4.42 |
Secondary
Sheehan Disability Scale (SDS)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolcapone | Sheehan Disability Scale (SDS) | -2.68 mean change in SDS score | Standard Deviation 4.41 |
| Placebo | Sheehan Disability Scale (SDS) | -1.97 mean change in SDS score | Standard Deviation 6.62 |