Guanfacine for Alcohol Use Disorder
Recruiting in Palo Alto (17 mi)
Overseen bySherry McKee, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yale University
Must not be taking: Anxiolytics, Antidepressants, CNS depressants, others
Disqualifiers: Hypertension, Hypotension, Substance use disorder, others
Prior Safety Data
Approved in 5 Jurisdictions
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.
12345Eligibility 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.
+6 more
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
+11 more
Trial 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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Guanfacine ERExperimental Treatment1 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: PlaceboPlacebo Group1 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, United States, European Union, European Union, Australia 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)
🇦🇺 Approved in Australia as Intuniv for:
- Attention Deficit Hyperactivity Disorder (ADHD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale University School of MedicineNew Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
References
Relationship Between Primary Care Providers' Perceptions of Alcohol Use Disorder And Pharmacotherapy Prescribing Rates. [2023]Acamprosate, naltrexone and disulfiram are underprescribed for alcohol use disorder (AUD) with marked variability among primary care providers (PCPs). We aimed to identify differences between high and low prescribers of medications for AUD (MAUD) with regard to knowledge, experiences, prioritization and attitudes.
Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.
Pharmacotherapy of alcoholism - an update on approved and off-label medications. [2018]Only a few medications are available for the treatment of alcohol use disorders (AUDs). Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants. Clinical implications, benefits and risks of treatment are discussed. Expert opinion: Acamprosate, naltrexone, nalmefene and disulfiram are the only approved 'alcohol-specific' drugs. Acamprosate and naltrexone have been evaluated in numerous clinical trials and represent evidence-based treatments in AUDs. Nalmefene use, however, is controversial. Supervised disulfiram is a second-line treatment approach. Compounds developed and licensed for different neuropsychiatric disorders are potential alternatives. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence. The GABA (γ-aminobutyric acid)-B receptor agonist baclofen has shown mixed results; it is currently licensed for the treatment of AUDs in France only. Gabapentin may be close to approval in the USA. Further studies of these novel treatment approaches in AUDs are needed.
Behavioral use of disulfiram in the treatment of problem drinking. [2019]As part of an outpatient treatment research project alternative ways of using Antabuse (disulfiram) in the treatment of problem drinkers are developed. Instead of forced regular use, Antabuse was administered as a voluntary situational therapeutic tool. Subjects were 84 men and 51 women. Thirty percent of both men and women decided to use Antabuse. Men most often used disulfiram continuously for a longer period or to stop an ongoing drinking period. The women used Antabuse to secure shorter periods of abstinence as part of their drinking schedules and to prevent drinking in specific high-risk situations. The subjects using Antabuse reduced their ethanol consumption significantly (p less than .05) at the end of the follow-up period, compared to the nonusers.
Nalmefene and its use in alcohol dependence. [2017]Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious.