Brexpiprazole for Alcoholism

Recruiting in Palo Alto (17 mi)

Overseen by Joseph P Schacht, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

Must not be taking: Psychoactive medications

Disqualifiers: Substance use disorder, Psychotic, Mood, others

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests whether brexpiprazole can help reduce alcohol consumption in people with Alcohol Use Disorder who are not seeking treatment. The medication works by balancing brain chemicals related to mood and behavior. Researchers will also see if genetic differences affect how well the medication works. Brexpiprazole is a newer medication related to aripiprazole, which has shown potential in reducing alcohol use by stabilizing dopamine and serotonin systems.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any current psychoactive medications, as the trial excludes participants who are currently using them.

What data supports the effectiveness of the drug Brexpiprazole for treating alcoholism?

While there is no direct evidence for Brexpiprazole in treating alcoholism, similar drugs like Aripiprazole, which also affects dopamine and serotonin systems, have shown some promise in reducing drinking behavior in alcoholics, although results have been inconsistent. ^{1 2 3 4 5}

How does the drug Brexpiprazole differ from other treatments for alcoholism?

Brexpiprazole is unique because it is an atypical antipsychotic that acts as a partial agonist at dopamine receptors, which may help reduce alcohol cravings and consumption by stabilizing the dopamine system involved in addiction. This mechanism is similar to aripiprazole, another drug studied for alcohol dependence, but Brexpiprazole's specific effects and efficacy in treating alcoholism are still being explored. ^{1 2 6 7 8}

Research Team

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for adults aged 21-65 with Alcohol Use Disorder who aren't seeking treatment and don't take medication for AUD. Participants must be physically healthy, live near the study site, have a negative drug screen, and not suffer from severe mental health disorders or significant medical illnesses.

Inclusion Criteria

Lives within 50 miles of the study site

Physically healthy with no history of significant medical illness

I am between 21 and 65 years old.

Exclusion Criteria

I have liver disease or my liver tests are higher than normal.

Insufficient English skills for consenting or interviews

I have had a head injury, lost consciousness for over 2 minutes, or had brain surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants are randomly assigned to take brexpiprazole or placebo for 14 days, with fMRI scans and assessments conducted

14 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Brexpiprazole (Serotonin/Dopamine Activity Modulator)

Trial Overview The trial tests Brexpiprazole's effectiveness in reducing alcohol consumption compared to a placebo. It also examines if genetic differences (DAT1 genotype) affect its efficacy. The study includes natural condition assessments and lab-based drinking tasks, supplemented by brain imaging studies.

Participant Groups

Group I: BREX 4mg Active Control 1 Intervention

The BREX 4mg group will start at the same dose as the BREX 2mg group and titrate up at the same rate, so the BREX 4mg Arm will take .5 mg of brexpiprazole on day 1-2, 1 mg on day 3-4, 2mg on day 5-6, and 4mg on day 7 to reach its final 4mg dose for days 7-14. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the medication orally each morning.

Group II: BREX 2mg Active Control 1 Intervention

The BREX 2mg group will start at the same dose at the BREX 4mg group and titrate up at the same rate, so the BREX 2mg Arm will take .5 mg of brexpiprazole on day 1-2, 1 mg on day 3-4, and 2mg on day 5, to reach its final 2mg dose for day 5-14. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the medication orally each morning.

Group III: Placebo Placebo Group 1 Intervention

Participants in this Arm will take a medically inert placebo. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the capsule orally each morning.

Brexpiprazole is already approved in Canada, Japan, Brazil for the following indications:

Approved in Canada as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia

Approved in Japan as Rexulti for:

• Schizophrenia

Approved in Brazil as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Dr. George F. Koob

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Executive Officer since 2014

PhD in Neurobiology from the Scripps Research Institute

Dr. Patricia Powell

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Medical Officer since 2015

MD from an accredited institution

Findings from Research

Aripiprazole, an atypical antipsychotic, shows potential in reducing alcohol consumption based on animal studies, suggesting it may help manage cravings and impulsive behaviors associated with alcohol dependence.

Clinical trials have produced mixed results regarding aripiprazole's effectiveness in treating alcoholism, indicating a need for more targeted studies to determine optimal dosing and its role in different subgroups of alcoholics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole: a drug with a novel mechanism of action and possible efficacy for alcohol dependence. Vergne, DE., Anton, RF.[2019]

In a 12-week study involving 295 patients with alcohol dependence, aripiprazole did not significantly increase the percentage of days abstinent compared to placebo (58.7% vs 63.3%), indicating similar efficacy in maintaining abstinence.

However, aripiprazole was associated with fewer drinks per drinking day and a greater reduction in a biomarker for heavy alcohol consumption, suggesting potential benefits in reducing alcohol intake, despite higher rates of discontinuation and adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence. Anton, RF., Kranzler, H., Breder, C., et al.[2022]

In a study involving 146 alcohol-dependent patients, extending naltrexone treatment from 12 to 24 weeks did not significantly improve drinking outcomes, such as days abstinent or heavy drinking days.

Low medication compliance during the second phase of the study affected drinking outcomes, indicating that ongoing support and monitoring may be necessary for effective treatment with naltrexone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone's suppressant effects on drinking are limited to the first 3 months of treatment. Davidson, D., Wirtz, PW., Gulliver, SB., et al.[2018]

Naltrexone, an opiate antagonist, has been shown in recent clinical trials to significantly reduce excessive alcohol consumption, addressing the need for effective treatments in alcohol dependence.

This medication is particularly important as it targets the high relapse rates that often occur in the early stages of alcohol treatment, making it a valuable option for individuals seeking recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone and the Treatment of Alcohol Dependence. Volpicelli, JR., Clay, KL., Watson, NT., et al.[2020]

In a study involving 128 young adults aged 18-25 who engaged in heavy drinking, naltrexone did not significantly reduce the number of heavy drinking days or increase abstinence compared to placebo.

However, naltrexone was effective in reducing the number of drinks consumed per drinking day and the percentage of days with high blood alcohol concentration (BAC), suggesting it can help lower drinking intensity among heavy drinkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of alcohol drinking in young adults by naltrexone: a double-blind, placebo-controlled, randomized clinical trial of efficacy and safety. O'Malley, SS., Corbin, WR., Leeman, RF., et al.[2022]

In a study with 18 healthy social drinkers, aripiprazole was found to increase the sedative effects of alcohol and decrease its euphoric effects, suggesting it may help reduce the reinforcing properties of alcohol.

The medication was well tolerated, with tiredness being the most common side effect, indicating a favorable safety profile for potential use in treating heavy drinking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of aripiprazole on subjective and physiological responses to alcohol. Kranzler, HR., Covault, J., Pierucci-Lagha, A., et al.[2021]

In a study involving 169 alcohol-dependent participants over 12 weeks, naltrexone significantly reduced alcohol consumption, especially when participants reported high levels of craving, compared to acamprosate.

The findings suggest that naltrexone is more effective than acamprosate in managing cravings and reducing drinking behavior, highlighting its potential as a key treatment for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do acamprosate or naltrexone have an effect on daily drinking by reducing craving for alcohol? Richardson, K., Baillie, A., Reid, S., et al.[2018]

In a study involving 75 alcohol-dependent subjects over 16 weeks, aripiprazole demonstrated a longer duration of abstinence compared to naltrexone, suggesting its potential effectiveness in maintaining alcohol-free periods.

While aripiprazole and naltrexone showed similar overall efficacy in preventing relapse, naltrexone was more effective in reducing craving scores, indicating that both medications may have complementary roles in treating alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. Martinotti, G., Di Nicola, M., Di Giannantonio, M., et al.[2022]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Aripiprazole: a drug with a novel mechanism of action and possible efficacy for alcohol dependence. [2019]

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

A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Naltrexone's suppressant effects on drinking are limited to the first 3 months of treatment. [2018]

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

Naltrexone and the Treatment of Alcohol Dependence. [2020]

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

Reduction of alcohol drinking in young adults by naltrexone: a double-blind, placebo-controlled, randomized clinical trial of efficacy and safety. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effects of aripiprazole on subjective and physiological responses to alcohol. [2021]

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

Do acamprosate or naltrexone have an effect on daily drinking by reducing craving for alcohol? [2018]

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

Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. [2022]