Tolcapone for Obsessive-Compulsive Disorder

Recruiting in Palo Alto (17 mi)

Overseen by Jon E Grant, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Chicago

Must not be taking: New psychotropics

Disqualifiers: Psychosis, Bipolar, Substance use, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing tolcapone, a medication that may help reduce symptoms of OCD by affecting dopamine levels in the brain. It targets adults with moderate to severe OCD who have significant symptoms. The study also looks at how tolcapone might improve thinking skills and whether genetic differences affect its effectiveness. Tolcapone has been investigated for its potential cognitive benefits in healthy adults.

Do I have to stop taking my current medications for this trial?

The trial allows stable doses of psychotropic medications, so you don't have to stop taking them if they have been stable for at least 3 months before the study.

What data supports the idea that Tolcapone for Obsessive-Compulsive Disorder is an effective drug?

The available research does not provide any data supporting the effectiveness of Tolcapone for Obsessive-Compulsive Disorder. The studies mentioned focus on other drugs and conditions, such as Alzheimer's disease and diabetic neuropathy, without mentioning Tolcapone's impact on Obsessive-Compulsive Disorder. ^{1 2 3 4 5}

What safety data is available for Tolcapone in treating OCD?

The provided research does not contain any safety data for Tolcapone or its other names related to the treatment of Obsessive-Compulsive Disorder. The studies focus on other medications like trospium chloride and tolterodine for overactive bladder, without mentioning Tolcapone. ^{6 7 8 9 10}

Is the drug Tolcapone a promising treatment for Obsessive-Compulsive Disorder?

The research articles mainly discuss Tolcapone's use in treating Parkinson's disease and major depressive disorder, but they do not provide specific evidence about its effectiveness for Obsessive-Compulsive Disorder. Therefore, based on the available information, we cannot conclude that Tolcapone is a promising treatment for Obsessive-Compulsive Disorder. ^{11 12 13 14 15}

Research Team

Jon E Grant, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults aged 18-65 with moderate to severe Obsessive Compulsive Disorder (OCD), evidenced by a YBOCS score of at least 21. Participants must understand and sign the consent form, not be pregnant or breastfeeding, have no alcohol/substance abuse issues, stable psychotropic medication use if any, normal liver function, and no major cognitive impairments.

Inclusion Criteria

YBOCS score of at least 21 at baseline (moderate or higher severity)

I am between 18 and 65 years old.

My primary diagnosis is OCD.

Exclusion Criteria

I am not pregnant, breastfeeding, and I use effective birth control.

I can understand and manage my medication, and I can give informed consent.

Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tolcapone or placebo for 8 weeks, with dosage adjustments after 2 weeks

8 weeks

Weekly visits (in-person)

Cognitive Assessment

Neuropsychological tasks conducted pre- and post-treatment to assess cognitive effects

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Tolcapone (Catechol-O-methyltransferase (COMT) Inhibitor)

Trial Overview The study is testing the effectiveness and safety of Tolcapone in treating OCD. Participants will either receive Tolcapone or a placebo to compare outcomes. The goal is to see if Tolcapone can help reduce the symptoms of OCD more effectively than a non-active treatment.

Participant Groups

Group I: Tolcapone Experimental Treatment 1 Intervention

100mg of tolcapone twice daily for two weeks, then 200mg tolcapone twice daily for the remaining six weeks.

Group II: Placebo Placebo Group 1 Intervention

100mg of placebo twice daily for two weeks, then 200mg of placebo twice daily for the remaining six weeks.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Pete Salzmann

University of Chicago

Chief Executive Officer since 2018

MD from University of Chicago’s Pritzker School of Medicine, MBA from Stanford University’s Graduate School of Business

Anh Nguyen

University of Chicago

Chief Medical Officer

MD from Rutgers New Jersey Medical School, MBA from University of Chicago

Findings from Research

In a study of 236 Alzheimer's patients, velnacrine showed a significant improvement in cognitive symptoms compared to placebo, with better scores on the Alzheimer's Disease Assessment Scale after two, four, and six weeks of treatment.

While velnacrine was effective for some patients, it also caused side effects, including liver enzyme elevation in 28% of patients and common cholinergic effects like diarrhea and nausea, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled study of velnacrine in Alzheimer's disease. Zemlan, FP., Keys, M., Richter, RW., et al.[2019]

A meta-analysis of 25 randomized controlled trials (RCTs) from 2000 to 2015 revealed that the placebo effect sizes for the Neuropsychiatric Inventory (NPI) have significantly increased over time, indicating that participants in recent studies show greater improvements compared to earlier ones.

From 2009 to 2015, the placebo group demonstrated a significant mean improvement in NPI scores, which suggests that future clinical trials for behavioral and psychological symptoms of dementia (BPSD) should use updated effect size estimates for accurate power calculations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation in Placebo Effect Sizes in Clinical Trials of Oral Interventions for Management of the Behavioral and Psychological Symptoms of Dementia (BPSD): A Systematic Review and Meta-Analysis. Hyde, AJ., May, BH., Xue, CC., et al.[2022]

The proposed group sequential design with hierarchical testing can improve clinical trial efficiency by allowing for the early termination of the placebo arm, which reduces the sample size needed for that group.

By reallocating unused sample size from the placebo group to the test and reference treatment groups, the study can enhance the power of the equivalence test without increasing the risk of false positives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Group sequential design and analysis of clinical equivalence assessment for generic nonsystematic drug products. Tsong, Y., Zhang, JJ., Wang, SJ.[2007]

In a 52-week study involving 57 patients with subclinical diabetic neuropathy, tolrestat significantly improved nerve function compared to placebo, with a notable increase in normalized squatting test results (25 patients on tolrestat vs. 6 on placebo).

Patients taking tolrestat also showed a significant improvement in vibration perception thresholds, while those on placebo experienced a deterioration, suggesting tolrestat's potential role in preventing diabetic neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolrestat in the primary prevention of diabetic neuropathy. Giugliano, D., Acampora, R., Marfella, R., et al.[2019]

In a 4-week study involving 242 patients with bladder issues, tolterodine at a dose of 2 mg twice daily significantly improved bladder capacity compared to placebo, indicating its efficacy in treating detrusor overactivity.

Tolterodine was found to be safe and well tolerated, with only 9% of patients reporting dry mouth as a mild to moderate side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group. Jonas, U., Höfner, K., Madersbacher, H., et al.[2019]

In a 12-week study involving 601 participants, a once-daily dose of 60 mg trospium chloride significantly improved symptoms of overactive bladder, including urinary frequency and urgency, compared to placebo.

Trospium was well-tolerated, with common side effects like dry mouth and constipation occurring at lower rates than typically seen with other anticholinergic medications, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once daily trospium chloride is effective and well tolerated for the treatment of overactive bladder: results from a multicenter phase III trial. Staskin, D., Sand, P., Zinner, N., et al.[2013]

In a 12-week study involving 658 patients, trospium chloride significantly reduced the average number of daily toilet voids and improved urgency and incontinence episodes, showing effectiveness as early as week 1.

Trospium chloride was found to be safe and well tolerated, with common side effects including dry mouth and constipation, indicating a favorable safety profile for treating overactive bladder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase III trial studying trospium chloride in patients with overactive bladder. Rudy, D., Cline, K., Harris, R., et al.[2013]

Tolterodine, used for treating overactive bladder, was found to significantly reduce REM sleep duration in individuals with one or more deficient CYP2D6 alleles, indicating a potential genetic influence on its effects.

In contrast, no significant cognitive side effects or changes in subjective sleep quality were observed in participants, suggesting that tolterodine is generally safe for cognitive function, especially in those with normal CYP2D6 metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tolterodine on sleep structure modulated by CYP2D6 genotype. Diefenbach, K., Jaeger, K., Wollny, A., et al.[2015]

A study involving 20 healthy male volunteers demonstrated that a new generic trospium chloride capsule (20 mg) is bioequivalent to the reference tablet (20 mg), with pharmacokinetic parameters such as Cmax and AUC values falling within the acceptable range of 80% to 125%.

The trial showed no significant differences in safety or efficacy between the two formulations, and no adverse events were reported, indicating that the generic version is a safe alternative to the branded product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and bioequivalence studies of trospium chloride after a single-dose administration in healthy Chinese volunteers. Zhang, R., Yuan, G., Li, R., et al.[2022]

Tolcapone, a novel COMT inhibitor, was well tolerated in healthy volunteers across a wide range of doses (5 to 800 mg) without significant adverse effects or changes in vital signs.

The drug effectively inhibited COMT activity in erythrocytes by over 80% at doses of 200 mg and higher, demonstrating dose-proportional pharmacokinetics and a rapid onset of action, suggesting its potential for further study in treating Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Dingemanse, J., Jorga, KM., Schmitt, M., et al.[2018]

Tolcapone is an effective treatment for patients with fluctuating Parkinson's disease when used alongside levodopa and a peripheral dopa-decarboxylase inhibitor, significantly improving motor fluctuations and reducing the need for levodopa.

The drug is generally well tolerated, with most side effects being related to dopaminergic activity, making it a suitable option for patients who do not respond to or are not candidates for other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolcapone: a review of its use in the management of Parkinson's disease. Keating, GM., Lyseng-Williamson, KA.[2018]

Tolcapone, a COMT inhibitor, showed a good oral bioavailability of approximately 60% and was rapidly absorbed, reaching peak plasma concentrations within about 2 hours after administration, indicating its potential effectiveness in treating conditions like Parkinson's disease.

Both oral and intravenous doses of tolcapone were well tolerated by the 16 healthy male volunteers in the study, and the drug demonstrated a strong relationship between plasma concentration and COMT inhibition, suggesting it could be a valuable adjunct therapy to levodopa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics after oral and intravenous administration of tolcapone, a novel adjunct to Parkinson's disease therapy. Jorga, KM., Fotteler, B., Heizmann, P., et al.[2019]

In a study of 21 adults with major depressive disorder, tolcapone treatment for 8 weeks resulted in significant reductions in depression scores, indicating its potential efficacy as a treatment for MDD.

Despite the promising results, 38% of participants experienced side effects leading to dropout, highlighting the need for further double-blind, placebo-controlled studies to confirm tolcapone's safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. Fava, M., Rosenbaum, JF., Kolsky, AR., et al.[2019]

Tolcapone, a COMT inhibitor, was well tolerated in elderly subjects at all tested doses (100-800 mg), with only minor gastrointestinal side effects noted at higher doses, indicating its safety for this population.

The study demonstrated that tolcapone significantly enhances the bioavailability of levodopa (1.6 to 2.5-fold increase), suggesting it could be an effective adjunct therapy for improving treatment outcomes in Parkinson's disease without developing tolerance over the week-long treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects. Dingemanse, J., Jorga, K., Zürcher, G., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Double-blind placebo-controlled study of velnacrine in Alzheimer's disease. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Variation in Placebo Effect Sizes in Clinical Trials of Oral Interventions for Management of the Behavioral and Psychological Symptoms of Dementia (BPSD): A Systematic Review and Meta-Analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Group sequential design and analysis of clinical equivalence assessment for generic nonsystematic drug products. [2007]

4. United States pubmed.ncbi.nlm.nih.gov

Tolrestat in the primary prevention of diabetic neuropathy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Impact of donepezil treatment for Alzheimer's disease on caregiver time. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two doses of tolterodine versus placebo in patients with detrusor overactivity and symptoms of frequency, urge incontinence, and urgency: urodynamic evaluation. The International Study Group. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Once daily trospium chloride is effective and well tolerated for the treatment of overactive bladder: results from a multicenter phase III trial. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Multicenter phase III trial studying trospium chloride in patients with overactive bladder. [2013]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of tolterodine on sleep structure modulated by CYP2D6 genotype. [2015]

10. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and bioequivalence studies of trospium chloride after a single-dose administration in healthy Chinese volunteers. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. [2018]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Tolcapone: a review of its use in the management of Parkinson's disease. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics after oral and intravenous administration of tolcapone, a novel adjunct to Parkinson's disease therapy. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. [2019]

15. Germany pubmed.ncbi.nlm.nih.gov

Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects. [2019]