Guanfacine for Alcohol Use Disorder

Overseen By Sabrina Coppola

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Anxiolytics, Antidepressants, CNS depressants, others

Disqualifiers: Hypertension, Hypotension, Substance use disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 6 weeks

160 Participants Needed

Trial Summary

What is the purpose of this trial?

For this protocol, the investigators plan to collect pilot data to examine sex differences in guanfacine's effect on 1) counteracting stress and stimulation based drinking behavior in the laboratory and 2) improving clinical outcomes during a subsequent treatment phase.

Will I have to stop taking my current medications?

The trial requires that participants do not use psychoactive drugs, including anxiolytics and antidepressants, within the past 30 days. Additionally, participants cannot be on any antihypertensive drugs, alpha adrenergic blockers, or CNS depressants. If you are taking any of these medications, you may need to stop before joining the trial.

How is the drug Guanfacine ER unique in treating alcohol use disorder?

Guanfacine ER is unique for alcohol use disorder because it is being repurposed from its original use for conditions like ADHD and hypertension (high blood pressure), offering a novel approach compared to the few existing alcohol-specific drugs. This drug may provide a new option for personalized treatment in the diverse population of individuals with alcohol use disorder. ^{1 2 3 4 5}

Research Team

Sherry McKee, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults aged 21-70 with alcohol use disorder, as defined by DSM V criteria. Participants must be English literate, able to take oral medication, and willing to reduce drinking. Excluded are those using psychoactive drugs or with significant mental health issues, cardiovascular problems, liver/renal impairment, or a history of severe alcohol withdrawal.

Inclusion Criteria

Laboratory sessions will be scheduled such that subjects will not have major responsibilities on the following day which might limit drinking during the self administration session (e.g., job interview, exam)

Meets DSM V criteria for current (past 6 months) alcohol use disorder or Drinking criteria: Males Drinks more than 14 drinks per week and exceeds 4 drinks per day at least twice per week; Females Drinks more than 7 drinks per week and exceeds 3 drinks per day at least twice per week. Must meet drinking criteria during a consecutive 30 day period prior to baseline

I am a male who drinks more than 14 drinks weekly and exceeds 4 drinks per day twice a week, or I am a female who drinks more than 7 drinks weekly and exceeds 3 drinks per day twice a week.

Exclusion Criteria

Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application

Meet DSM V criteria for current (past 6 month) ADHD

Current DSM V substance use disorder, other than alcohol abuse disorder or nicotine dependence

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Titration

Titration to steady state medication levels over a 3 week period

3 weeks

Weekly visits (in-person)

Laboratory Sessions

Three laboratory sessions to evaluate ad lib alcohol consumption with personalized imagery

1 week

3 visits (in-person)

Treatment

Participants receive guanfacine or placebo combined with medical management at weekly appointments

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations at 1 and 3 months

3 months

2 visits (in-person)

Treatment Details

Interventions

• Guanfacine ER
• Placebo

Trial Overview The study tests whether Guanfacine ER can help control stress-induced and stimulation-based drinking behaviors in men and women with alcohol use disorders. It also looks at how it affects their overall treatment outcomes compared to a placebo.

Participant Groups

Group I: Guanfacine ER Experimental Treatment 1 Intervention

Guanfacine extended release (6mg/day ER). Administered orally twice daily at 8:00 AM and 8:00 PM while titrating to the full dose. Titration schedule: Days 1-3 1mg/day; 0.5mg/dose, Days 4-6 2mg/day; 1mg/dose, Days 7-9 3mg/day; 1.5mg/dose, Days 10-12 4mg/day; 2mg/dose; Days 13-15 5mg/day; 2.5mg/dose and Days 16-23 6mg/day; 3mg/dose. Once at steady state, administration is orally once per day at 8:00 PM.

Group II: Placebo Placebo Group 1 Intervention

Administered orally twice a day at 8:00 AM and 8:00 PM Days 1-23, then orally once a day at 8:00 PM.

Guanfacine ER is already approved in United States, European Union for the following indications:

Approved in United States as Tenex for:

• Hypertension

Approved in United States as Intuniv for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Intuniv for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Paxneury for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

High prescribers of medications for alcohol use disorder (AUD) demonstrated a more favorable view of the effectiveness of these medications compared to low prescribers, indicating that attitudes towards treatment efficacy can influence prescribing behavior.

PCPs with positive attitudes towards AUD treatment had a significantly higher prescribing rate (5.0%) compared to those with negative attitudes (1.9%), suggesting that improving attitudes may be crucial for increasing the use of medications like acamprosate, naltrexone, and disulfiram.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship Between Primary Care Providers' Perceptions of Alcohol Use Disorder And Pharmacotherapy Prescribing Rates. Bernstein, EY., Pfoh, ER., Le, P., et al.[2023]

Alcohol use disorder (AUD) is common but often under-treated, with only three approved medications, highlighting the need for more diverse and effective treatment options.

The review discusses various pharmacotherapies, including both approved and novel agents, showing promise for improving treatment efficacy and supporting personalized medicine approaches for individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Burnette, EM., Nieto, SJ., Grodin, EN., et al.[2022]

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 135 participants (84 men and 51 women), Antabuse (disulfiram) was used voluntarily as a situational tool rather than being forced, leading to significant reductions in alcohol consumption (p < .05) among users compared to nonusers.

Men tended to use Antabuse continuously or to stop drinking episodes, while women preferred it for shorter abstinence periods and to avoid drinking in high-risk situations, highlighting different usage patterns based on gender.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral use of disulfiram in the treatment of problem drinking. Duckert, F., Johnsen, J.[2019]

Nalmefene is the first drug approved in the E.U. specifically to reduce alcohol consumption in alcohol-dependent patients, showing significant efficacy over 6 months by reducing total alcohol intake by an average of 7.6 g/day and heavy drinking days by 2 days per month.

The drug is generally well tolerated with good compliance rates (over 80% adherence) among patients using it as needed, making it a promising new approach in treating alcohol dependence alongside brief psychosocial interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nalmefene and its use in alcohol dependence. Gual, A., Bruguera, P., López-Pelayo, H.[2017]

References

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

Relationship Between Primary Care Providers' Perceptions of Alcohol Use Disorder And Pharmacotherapy Prescribing Rates. [2023]

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

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]

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

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

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

Behavioral use of disulfiram in the treatment of problem drinking. [2019]

5. Spain pubmed.ncbi.nlm.nih.gov

Nalmefene and its use in alcohol dependence. [2017]