Brexpiprazole for Alcoholism

Overseen By Kristen M Raymond

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Psychoactive medications

Disqualifiers: Substance use disorder, Psychotic, Mood, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 14 days

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, brexpiprazole, to determine if it can reduce drinking in people with Alcohol Use Disorder (AUD). Researchers aim to discover if the drug is more effective in individuals with specific genetic variations related to the dopamine transporter gene. Participants will receive either a low dose, a higher dose, or a placebo (a pill with no active medication). Individuals diagnosed with AUD who are not currently seeking treatment or taking medication for it might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that brexpiprazole is likely to be safe for humans?

Research has shown that brexpiprazole is generally safe for people. Studies have found it effective in treating several mental health conditions, such as schizophrenia. Common side effects include weight gain and restlessness, but these are usually mild to moderate.

In studies for other conditions, serious side effects were rare. The FDA has already approved brexpiprazole for some mental health conditions, indicating it has passed strict safety tests for those uses.

The current study on brexpiprazole for alcohol use disorder remains in an early stage. Early-stage trials often focus on safety, so participation helps confirm how well the medication is tolerated for new uses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Brexpiprazole is unique because it offers a different approach to treating alcoholism by targeting both dopamine and serotonin receptors in the brain. Traditional treatments often focus on just one aspect of brain chemistry, but brexpiprazole's dual action might help reduce alcohol cravings and improve mood stability more effectively. Researchers are excited about this potential because it could offer a more comprehensive solution for people struggling with alcoholism, who currently rely on options like disulfiram, naltrexone, and acamprosate. By addressing multiple pathways in the brain, brexpiprazole could potentially enhance treatment outcomes and provide relief more quickly.

What evidence suggests that brexpiprazole might be an effective treatment for alcoholism?

Studies have shown that brexpiprazole can significantly reduce symptoms in people with certain mental health conditions, such as schizophrenia, by affecting brain chemicals like serotonin and dopamine. This trial aims to evaluate brexpiprazole's potential to reduce alcohol consumption in people with Alcohol Use Disorder (AUD). Although specific data on brexpiprazole for AUD is still emerging, its ability to influence brain pathways involved in addiction appears promising. Initial findings in related conditions, where brexpiprazole improved outcomes, offer a hopeful outlook for its potential in treating AUD. Participants in this trial will receive either a 2mg or 4mg dose of brexpiprazole, or a placebo, to assess its effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Joseph P Schacht, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Brexpiprazole

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.

How Is the Trial Designed?

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 United States, Canada, European Union, Japan, Brazil for the following indications:

Approved in United States as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia
• Agitation associated with dementia due to Alzheimer's disease

Approved in Canada as Rexulti for:

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

Approved in European Union as Rexulti for:

• 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+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

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]

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 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 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]

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]

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 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 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]

Citations

1. withpower.com withpower.com/trial/phase-3-alcohol-drinking-9-2020-0efcd

Brexpiprazole for Alcoholism This trial tests whether brexpiprazole can help reduce alcohol consumption in people with Alcohol Use Disorder who are not seeking treatment.

2. mdpi.com mdpi.com/1424-8247/17/4/535

Investigating the Effectiveness of Brexpiprazole in Subjects ... Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001).

3. researchgate.net researchgate.net/publication/377548876_Investigating_the_Effectiveness_of_Brexpiprazole_in_Schizophrenic_Patients_with_Concurrent_Alcohol_and_Substance_Use_Disorder_A_Prospective_Multicentric_Real-World_Study

(PDF) Investigating the Effectiveness of Brexpiprazole in ... Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8366183/

Two randomized, double-blind, placebo-controlled trials ... This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081)

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04066192/brexpiprazole-in-alcohol-use-disorder

Brexpiprazole in Alcohol Use Disorder This study will evaluate the effects of two doses of BREX, relative to placebo, among non-treatment-seeking individuals with AUD, and will test ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK535490/

References - Clinical Review Report: Brexpiprazole (Rexulti) A phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of brexpiprazole (OPC-34712) as ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/205422Orig1s009MultidisciplineR.pdf

205422Orig1s009 - accessdata.fda.gov Discussion: Although favorable safety data comparing brexpiprazole to alternative treatments could further justify brexpiprazole's benefit ...