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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how guanfacine, a medication, can help individuals with alcohol use disorder manage stress-related drinking and improve overall drinking habits. Participants will receive either guanfacine or a placebo to determine any differences in drinking behavior. The trial seeks individuals who have been drinking heavily for at least the past six months and are open to reducing their alcohol intake. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that guanfacine ER is generally well-tolerated. Other studies report common side effects such as sleepiness, headaches, and fatigue among those taking guanfacine ER. These side effects occurred more frequently than in those taking a placebo, but not everyone experienced them.

Guanfacine ER also treats ADHD (attention-deficit/hyperactivity disorder) in children and teens. In these cases, it has been associated with drops in blood pressure and heart rate, so caution is advised for those at risk. However, for most, these changes are not serious.

The approval of guanfacine ER for treating ADHD provides some reassurance about its safety. As this trial is in the early stages, it primarily aims to assess how well participants tolerate the medication. While some evidence supports its safety, the trial will gather more specific information on its use for alcohol use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Guanfacine ER for alcohol use disorder because it offers a novel approach to treatment. Unlike traditional options like naltrexone, disulfiram, or acamprosate, which primarily target cravings or induce adverse reactions to alcohol, Guanfacine ER works by modulating the adrenergic system, potentially reducing stress and impulsive behavior associated with alcohol use. This new mechanism of action could be particularly beneficial for individuals who haven't responded well to existing treatments. Additionally, the extended-release formulation ensures a stable release of the medication, which could improve adherence and overall efficacy.

What evidence suggests that guanfacine ER might be an effective treatment for alcohol use disorder?

Research has shown that guanfacine ER, which participants in this trial may receive, might help reduce alcohol consumption. In studies with rats, guanfacine significantly reduced alcohol intake, suggesting potential benefits for people as well. Some research indicates it might be more effective for women by reducing cravings and improving self-control. Although more studies are needed, early results are promising for those dealing with alcohol use disorder. Participants in this trial may also receive a placebo as part of the study's control arm. ^{1 2 6 7 8}

Who Is on the Research Team?

Sherry McKee, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. grantome.com grantome.com/grant/NIH/R21-AA024880-02

Guanfacine to reduce relapse risk in women with alcohol ... Our prior research shows that guanfacine may preferentially reduce craving and improve cognitive control in women with AUD, compared to men. As these behaviors ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25359257/

Evaluation of guanfacine as a potential medication for ... Guanfacine decreased alcohol intake in high, but not low, alcohol-consuming rats and the effects were generally more long lasting than that of the AUD ...

3. journals.lww.com journals.lww.com/ccmjournal/fulltext/2022/01001/980__evaluation_of_guanfacine_use,_safety,_and.946.aspx

980: evaluation of guanfacine use, safety, and efficacy for ... There were 17 patients with a positive ICDSC screening prior to the first dose of guanfacine and 65% of these patients had a negative screen at the time of drug ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4367455/

Evaluation of Guanfacine as a Potential Medication for Alcohol ... In this study, both guanfacine and the AUD medication naltrexone significantly decreased voluntary alcohol intake in long-term-drinking rats.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06629259

NCT06629259 | Guanfacine for Alcohol Use Disorder (AUD) This is a study to examine the efficacy of guanfacine extended release (GXR) (3mg/d) compared with placebo (PBO) in reducing drinking in N=200 men and women ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2935643/

Guanfacine Extended-Release Tablets (Intuniv), a ... Common side effects reported more often in patients who received guanfacine ER, compared with placebo, included somnolence, headache, and fatigue. No ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf

INTUNIV (guanfacine) extended-release tablets Hypotension, bradycardia, and syncope: Use INTUNIV® with caution in patients at risk for hypotension, bradycardia, heart block, or syncope (e.g., those taking ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X14002788

Efficacy and safety of extended-release guanfacine ... This study assessed the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.