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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

For this protocol, the investigators plan to conduct a pilot study evaluating the effect of propranolol on alcohol consumption. Using a parallel design, the investigators plan to randomize 20 non-treatment seeking adults with alcohol use disorders (DSM-5) to propranolol extended release (160mg/day or placebo; n=10 per cell) to evaluate whether propranolol reduces alcohol self-administered in the laboratory. Importantly, the investigators will evaluate whether propranolol counteracts stress-induced effects on alcohol self-administration. Following titration to steady state medication levels over a 2-week period, each subject will complete two laboratory sessions consisting of a well validated method for inducing stress or neutral/relaxing state (order counterbalanced), followed by a 2-hour alcohol self-administration paradigm known to be sensitive to medication effects.

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.

What safety data exists for propranolol in treating alcohol use disorders?

The safety data for propranolol, under various formulations like Inderal and Inderal LA, has been evaluated in studies for conditions such as migraine and anxiety. Common side effects include drowsiness, fatigue, dizziness, and indigestion, which were generally mild. In a study comparing propranolol with chlordiazepoxide and placebo for anxiety, the incidence of side effects was similar between propranolol and chlordiazepoxide, with some side effects more frequent in each group compared to placebo. No significant differences in pharmacokinetic and pharmacodynamic parameters were observed among different brands of propranolol. These studies suggest that propranolol is generally well-tolerated, but specific safety data for alcohol use disorders is not directly available from the provided studies. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol has been studied for various conditions, and common side effects include drowsiness, fatigue, and dizziness, which are generally mild. In studies, the incidence of side effects was similar to placebo, indicating it is generally safe for human use. ^{1 2 3 4 5}

Is propranolol a promising drug for alcohol use disorders?

Propranolol is a drug that has shown promise in treating various conditions like migraines, high blood pressure, and heart issues. It is available in different forms and brands, and studies suggest it can be effective in managing symptoms over a long period. However, there is no specific information in the provided research about its effectiveness for alcohol use disorders. ^{1 3 4 6 7}

How does the drug propranolol differ from other treatments for alcohol use disorders?

Propranolol is unique because it is a beta blocker, typically used for heart-related conditions, that may help with alcohol use disorders by reducing anxiety and stress, which are often triggers for alcohol consumption. Its long-acting formulation allows for once-daily dosing, which can improve patient convenience and adherence compared to treatments requiring multiple doses per day. ^{1 3 4 6 7}

What data supports the idea that Propranolol for Alcohol Use Disorders is an effective drug?

The available research shows that propranolol may help with symptoms related to alcohol use disorders. 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 symptoms of psychic tension. Another study on rats indicated that higher doses of propranolol reduced alcohol drinking. However, the research is limited, and propranolol's effectiveness compared to other treatments for alcohol use disorders is not well-established. ^{1 2 4 8 9}

What data supports the effectiveness of the drug propranolol for alcohol use disorders?

Research suggests that propranolol, a drug that affects the body's stress response, may help reduce alcohol consumption in animal studies. Additionally, propranolol has been shown to calm symptoms in people with alcohol withdrawal, indicating potential benefits for alcohol use disorders. ^{1 2 4 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

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]

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 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]

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]

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]

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 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]

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]

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]

Citations

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

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. [2017]

2. England pubmed.ncbi.nlm.nih.gov

The role of beta- and alpha-adrenergic receptors on alcohol drinking. [2023]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

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

Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial. [2022]

6. England 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. [2019]

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

Propranolol in chronic anxiety disorders. A controlled study. [2022]

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

Stability of propranolol hydrochloride in SyrSpend SF. [2022]

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

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