Propranolol for Alcohol Use Disorders

Overseen By Paula Cunningham

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Disqualifiers: Significant medical conditions, Pregnancy, Mental illness, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether propranolol, a medication often used for heart issues, can help people with alcohol use disorders reduce their alcohol consumption. Researchers aim to determine if propranolol can lower alcohol intake, particularly during stress. Participants will receive either propranolol or a placebo, and their alcohol consumption will be monitored in a controlled setting. The trial seeks adults who have dealt with alcohol use issues for the past six months and are not actively seeking treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be able to take oral medications and adhere to the medication regimen for the trial.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that propranolol is commonly used to treat high blood pressure and heart rhythm problems, and most people tolerate it well. Past studies identified tiredness, dizziness, and nausea as the usual side effects, which are generally mild and tend to resolve on their own.

Drinking alcohol while taking propranolol can increase the likelihood of dizziness or lightheadedness. This is important for those considering participation in a trial involving both propranolol and alcohol.

The dose used in this trial is similar to that typically used for high blood pressure, suggesting that its safety profile will be comparable to other uses of the drug. It is important to discuss any concerns with the trial team or a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for alcohol use disorders, which often include medications like naltrexone, acamprosate, and disulfiram, propranolol offers a novel approach. Propranolol is traditionally used to manage heart conditions and anxiety, but researchers are exploring its potential to target the stress-related components of alcohol cravings. What's unique about propranolol is its ability to modulate the adrenergic system, potentially reducing the urge to drink by dampening the body's stress response. This makes it an exciting candidate for addressing the psychological triggers of alcohol use disorder in a new way.

What evidence suggests that propranolol might be an effective treatment for alcohol use disorders?

Research has shown that propranolol, which participants in this trial may receive, might help individuals with alcohol use problems. One study found that propranolol reduced the urge to drink by affecting how the brain refreshes old memories. Another study demonstrated that propranolol decreased the desire to seek alcohol in participants. Additionally, propranolol proved more effective than diazepam at calming patients during alcohol withdrawal. These findings suggest that propranolol might help reduce both the craving for alcohol and drinking, especially under stress. ^{1 6 7 8 9}

Who Is on the Research Team?

Sherry McKee, PhD

Principal Investigator

Professor

Are You a Good Fit for This Trial?

This trial is for adults aged 21-65 who have been diagnosed with alcohol use disorders in the last 6 months, can read and write English, and are willing to take oral medication regularly. It's not suitable for those at risk of severe alcohol withdrawal, with serious health issues, pregnant or nursing women not using effective birth control, or individuals with recent mental illness.

Inclusion Criteria

I can take pills and will follow the medication plan.

I am between 21 and 65 years old.

Able to read and write English

Exclusion Criteria

Suicidal, homicidal, or evidence of current mental illness

Subjects likely to exhibit clinically significant alcohol withdrawal during the study

I am not pregnant, nursing, and I use approved birth control methods.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants titrate to steady state medication levels over a 2-week period

2 weeks

Daily medication administration

Laboratory Sessions

Participants complete two laboratory sessions with stress or neutral/relaxing state induction followed by a 2-hour alcohol self-administration paradigm

1 week

2 laboratory visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Propranolol

Trial Overview The study tests if Propranolol (a beta blocker) at a dose of 160mg/day can reduce stress-induced alcohol consumption compared to a placebo. Participants will undergo two lab sessions after a two-week period of taking the drug to see how it affects their drinking behavior under induced stress versus a relaxed state.

How Is the Trial Designed?

Group I: Propranolol Experimental Treatment 1 Intervention

Propranolol extended release (160mg/day). Administered orally once daily at 10:00PM. Titration schedule Days 1-3 60mg, Days 4-7 80mg, Days 8-11 120mg, and Days 12-14 160mg until steady state.

Group II: Placebo Placebo Group 1 Intervention

Administered orally once daily at 10:00PM

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

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

Propranolol hydrochloride, a beta blocker used for various heart-related conditions, can be effectively compounded into a stable 1-mg/mL suspension using SyrSpend SF, making it a viable option for patients who cannot tolerate oral tablets or capsules.

The study demonstrated that this compounded suspension remains stable for at least 90 days when stored in a low-actinic plastic bottle at room temperature, ensuring its efficacy and safety for patient use during this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of propranolol hydrochloride in SyrSpend SF. Geiger, CM., Voudrie, MA., Sorenson, B.[2022]

In a study involving 51 patients, both long-acting formulations of propranolol significantly reduced the frequency of migraine attacks compared to placebo, demonstrating their efficacy in migraine management.

The higher dose formulation (Inderal LA 160 mg) was more effective than the lower dose (Half-Inderal LA 80 mg) in reducing migraine frequency, with no significant difference in side effects between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. Carroll, JD., Reidy, M., Savundra, PA., et al.[2017]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

In a study using male Wistar rats, the β1/2 adrenergic receptor antagonist propranolol significantly reduced alcohol drinking, particularly showing a trend towards greater impact on compulsion-like alcohol drinking (CLAD) compared to alcohol-only drinking (AOD).

While propranolol and betaxolol showed potential in decreasing alcohol consumption, they may also cause undesirable side effects, and their effects on specific brain areas related to drinking did not yield expected results, suggesting a complex role of the noradrenergic system in alcohol use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of beta- and alpha-adrenergic receptors on alcohol drinking. De Oliveira Sergio, T., Wean, S., Katner, SN., et al.[2023]

In a double-blind crossover study involving 26 patients with chronic anxiety disorders, propranolol hydrochloride effectively reduced symptoms in 17 patients, indicating its potential as a treatment option.

While propranolol showed benefits in alleviating both physical and psychological symptoms of anxiety, the side effects were mostly mild and similar to anxiety symptoms, and its efficacy compared to other anti-anxiety medications remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol in chronic anxiety disorders. A controlled study. Kathol, RG., Noyes, R., Slymen, DJ., et al.[2022]

In patients undergoing withdrawal from chronic alcoholism, propranolol effectively normalizes increased cardiac output and reduces peripheral vascular resistance, leading to a calming effect, as observed in a double-blind study.

Propranolol was found to be more effective than diazepam in alleviating symptoms of psychic tension associated with alcohol withdrawal, with minimal side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol in the treatment of alchoholism: a review. Carlsson, C.[2013]

In a 3-week study involving 212 patients, both propranolol and chlordiazepoxide significantly reduced anxiety levels compared to placebo, with propranolol showing superior efficacy by Week 2.

While both medications had similar side effect profiles, chlordiazepoxide was associated with more fatigue and drowsiness, while propranolol had higher reports of drowsiness and indigestion compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial. Meibach, RC., Dunner, D., Wilson, LG., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12057275/

Effect of inhibition of reactivated alcohol-associated memories ... The findings revealed that propranolol administration during memory reconsolidation could reduce alcohol craving in alcohol-dependent patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2966867/

Effects of β-adrenoceptor antagonists on alcohol drinking by ... Propranolol suppressed PR operant alcohol-reinforced responding across groups, an effect attributable to significant suppression of alcohol responding at the ...

3. withpower.com withpower.com/trial/phase-3-alcohol-drinking-8-2018-50c48

Propranolol for Alcohol Use Disorders · Info for Participants In one study, propranolol was found to calm patients during the withdrawal phase of chronic alcoholism, and it was more effective than diazepam in reducing ...

4. mdpi.com mdpi.com/1422-0067/23/17/10099

Propranolol versus Other Selected Drugs in the Treatment ... Propranolol administered within the first 6 h after a traumatic event significantly reduces the likelihood of developing PTSD [59,60]. This drug appeared to be ...

5. yalemedicine.org yalemedicine.org/clinical-trials/does-propanolol-a-beta-blocker-attenuate-stress-induced-drinking

Does Propanolol, a Beta Blocker, Attenuate Stress-Induced ... The investigators will evaluate whether propranolol counteracts stress-induced effects on alcohol self-administration.

6. drugs.com drugs.com/propranolol.html

Propranolol: Uses, Dosage, Side Effects, Warnings Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory ...

7. webmd.com webmd.com/drugs/2/drug-10404-9168/propranolol-oral/propranolol-oral/details

Propranolol (Inderal LA, Innopran XL, others) - Uses, Side ... Drinking alcohol may increase the drug levels of propranolol and may increase risk of side effects. Does propranolol interact with other ...

8. goodrx.com goodrx.com/drugs/safety/medications-to-not-mix-with-alcohol?srsltid=AfmBOoqDeImLTLk5h0dUWouvNQGZuHB2vjWdAhL9lYFbpUqVBEfAaazF

14 Medications You Shouldn't Mix With Alcohol This can leave you at a higher risk of intoxication and alcohol poisoning. 13. Propranolol (Inderal, InnoPran XL, Hemangeol). Propranolol (Inderal, InnoPran XL, ...

9. reference.medscape.com reference.medscape.com/drug/inderal-inderal-la-propranolol-342364

Inderal, Inderal LA (propranolol) dosing, indications, ... Indicated for management of hypertension. Immediate release: 40 mg PO q12hr initially, increasing every 3-7 days; maintenance: 80-240 mg PO q8-12hr; not to ...