Tolcapone for Alcoholism and ADHD

Overseen By Kristen Raymond, BA

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests tolcapone to see if it helps people with both alcohol use issues and attention problems. The study focuses on people with both AUD and ADHD. Tolcapone works by affecting brain chemicals related to mood and behavior. Initially used for Parkinson's disease, tolcapone might be considered for ADHD treatment.

Do I have to stop taking my current medications to join the trial?

Yes, you must not be taking any medication for AUD, ADHD, or any psychoactive medication to participate in this trial.

What data supports the idea that Tolcapone for Alcoholism and ADHD is an effective drug?

The available research shows that Tolcapone has been studied primarily for its use in treating Parkinson's disease, not Alcoholism or ADHD. The studies focus on its ability to help manage symptoms in Parkinson's patients by improving 'on' time and reducing 'off' time when used with other medications. There is no data provided that supports its effectiveness for Alcoholism or ADHD. ^{1 2 3 4 5}

What safety data exists for Tolcapone in treating alcoholism and ADHD?

The provided research does not contain safety data for Tolcapone or its other names (Tasmar, Tolcapon, etc.) in the treatment of alcoholism and ADHD. The studies focus on other medications like nalmefene and naltrexone for alcohol dependence. Further research specifically on Tolcapone is needed to answer this question. ^{6 7 8 9 10}

Is the drug Tolcapone a promising treatment for Alcoholism and ADHD?

Tolcapone shows potential as a treatment for Alcohol Use Disorder, especially in individuals who are physically dependent on alcohol, as it may help reduce alcohol consumption. However, its effectiveness for ADHD is not discussed in the provided research. ^{1 4 5 11 12}

Research Team

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults aged 21-65 who meet the criteria for both Alcohol Use Disorder (AUD) and Attention-Deficit/Hyperactivity Disorder (ADHD), but are not currently seeking treatment or taking medication for these conditions. Participants must live within 50 miles of the study site, be able to understand consent forms, and not have any severe medical issues or metal in their body.

Inclusion Criteria

Currently not engaged in, and does not want treatment for, AUD or ADHD

You currently meet the criteria for Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder according to specific diagnostic assessments.

I am between 21 and 65 years old.

Exclusion Criteria

Current charges pending for a violent crime (not including DUI-related offenses)

I am not pregnant, nursing, and I use reliable contraception.

I have been diagnosed with a mental health disorder like schizophrenia, depression, or an eating disorder.

Treatment Details

Interventions

• Placebo (Other)
• Tolcapone (COMT Inhibitor)

Trial Overview The study tests if tolcapone, a drug that affects brain chemistry, changes how people with AUD/ADHD respond to alcohol, make decisions, react to alcohol cues in the brain, control impulses and focus attention compared to a placebo. It also looks at whether it affects their drinking habits.

Participant Groups

Group I: Tolcapone then Placebo Experimental Treatment 2 Interventions

Participants in this arm will receive tolcapone during the first medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8), and placebo during the second medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8).

Group II: Placebo then Tolcapone Experimental Treatment 2 Interventions

Participants in this arm will receive placebo during the first medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8), and tolcapone during the second medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8).

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

Tolcapone is an effective adjunct treatment for Parkinson's disease, significantly reducing 'off' time and improving symptoms in patients who do not respond to other therapies, with a recommended dosage of 100 mg three times daily.

However, tolcapone carries risks of serious side effects, including potential liver damage, necessitating regular liver function tests and careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolcapone: a novel approach to Parkinson's disease. Micek, ST., Ernst, ME.[2019]

In two large studies involving 379 patients with Parkinson's disease, tolcapone at doses of 300 and 600 mg/day significantly improved 'on' time and reduced 'off' time, indicating better motor function while on levodopa treatment.

While tolcapone was effective in enhancing motor control, the most common side effect was increased dyskinesia, although hallucinations were rare, suggesting a need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highlights of the North American and European experiences. Goetz, CG.[2019]

Tolcapone significantly increased the plasma levels of levodopa in healthy volunteers, effectively doubling the area under the plasma concentration-time curve and extending the half-life of levodopa, particularly at a 200 mg dose.

The study found that tolcapone was well-tolerated with only minor adverse effects across all tested doses, suggesting it is a safe add-on therapy for enhancing levodopa efficacy in Parkinson's disease treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers. Sêdek, G., Jorga, K., Schmitt, M., et al.[2019]

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]

Bromocriptine is the standard treatment for motor fluctuations in Parkinson's patients on levodopa, while the efficacy of entacapone compared to bromocriptine remains unclear, as no significant benefits were found for tolcapone over entacapone.

Tolcapone, although reintroduced to the market, has a negative risk-benefit balance due to serious potential side effects, including liver damage, and does not show significant efficacy compared to other treatments like bromocriptine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis. [2013]

Nalmefene shows limited efficacy in reducing alcohol consumption among adults with alcohol dependence, with a significant reduction in the number of heavy drinking days compared to placebo, but no substantial differences in mortality or quality of life outcomes.

The analysis revealed a higher rate of withdrawals due to safety concerns in the nalmefene group compared to placebo, indicating potential safety issues that need to be considered when evaluating its use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials. Palpacuer, C., Laviolle, B., Boussageon, R., et al.[2018]

Nalmefene, used as needed for alcohol dependence, was generally well-tolerated among patients, with 74.7% experiencing treatment-emergent adverse events (TEAEs) compared to 62.7% in the placebo group, indicating a manageable safety profile.

Despite a higher dropout rate due to TEAEs in the nalmefene group (13.0% vs. 5.9% for placebo), no significant safety concerns were identified, including no increased risk of suicide-related behavior, suggesting nalmefene can be a viable option for reducing alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme. van den Brink, W., Strang, J., Gual, A., et al.[2015]

Acamprosate and naltrexone are the only two medications approved for treating alcohol use disorders (AUDs) that have strong evidence from numerous clinical trials, making them effective options for patients.

Several off-label medications, such as topiramate and gabapentin, show promise for treating AUDs, but more research is needed to confirm their efficacy and safety in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcoholism - an update on approved and off-label medications. Soyka, M., Müller, CA.[2018]

In a study involving 36 older adults (over 50 years) with alcohol dependence, naltrexone was found to be well tolerated, showing no significant differences in adverse effects compared to a placebo group.

While naltrexone did not produce clinically significant adverse effects, its efficacy in treating alcohol dependence in this age group remains to be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of naltrexone in treating older, alcohol-dependent patients. Oslin, D., Liberto, JG., O'Brien, J., et al.[2016]

In a 12-week study involving 378 adults with alcohol dependence, those taking nalmefene as needed significantly reduced their heavy drinking days by an average of 13.1 days per month, demonstrating its efficacy in lowering alcohol consumption.

The treatment was well tolerated, with common side effects including nausea (18.3%) and dizziness (17.7%), indicating that nalmefene can be a safe option for managing alcohol dependence in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care. Castera, P., Stewart, E., Großkopf, J., et al.[2019]

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]

Tolcapone, a COMT inhibitor, significantly reduced ethanol self-administration in alcohol-dependent rats, suggesting its potential as a targeted treatment for Alcohol Use Disorder (AUD).

The study found that tolcapone did not affect drinking behavior in non-dependent rats or those consuming saccharin, indicating its effects are specific to alcohol dependence, and its efficacy varied based on the estrous cycle in female rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats. Doyle, MR., Dirik, S., Martinez, AR., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Tolcapone: a novel approach to Parkinson's disease. [2019]

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

Highlights of the North American and European experiences. [2019]

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

Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers. [2019]

4. 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]

5. France pubmed.ncbi.nlm.nih.gov

Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis. [2013]

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

Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of as-needed nalmefene in the treatment of alcohol dependence: results from the Phase III clinical programme. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcoholism - an update on approved and off-label medications. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Tolerability of naltrexone in treating older, alcohol-dependent patients. [2016]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care. [2019]

11. 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]

12. England pubmed.ncbi.nlm.nih.gov

Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats. [2023]