Propranolol for Obstructive Sleep Apnea

(ProSAT Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Calcium blockers, Sympatholytics, Anti-arrhythmics, others

Disqualifiers: Cardiovascular risks, Sleep disorders, Diabetes, 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: 2

Duration: 1 week

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking certain drugs like calcium channel blockers, other beta blockers, or specific anti-arrhythmic drugs. If you're on these medications, you won't be asked to stop them for the study.

What data supports the effectiveness of the drug propranolol for obstructive sleep apnea?

There is no direct evidence from the provided research articles supporting the effectiveness of propranolol for obstructive sleep apnea. However, propranolol is known to cause hypersomnolence (excessive sleepiness) in some cases, which might indirectly suggest a potential impact on sleep-related conditions. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol, used for various conditions, can cause side effects like excessive sleepiness and slow heart rate, but these are generally mild. It has been used safely in treating conditions like high blood pressure and anxiety, with common side effects including dizziness and fatigue. ^{2 3 5 6 7}

How does the drug propranolol differ from other treatments for obstructive sleep apnea?

Propranolol is unique because it is a beta-blocker that can cause hypersomnolence (excessive sleepiness), which might be beneficial for obstructive sleep apnea by promoting sleep. Additionally, the long-acting formulation of propranolol allows for a simplified dosing schedule, potentially improving patient convenience and compliance. ^{2 3 8 9 10}

What is the purpose of this trial?

This trial tests whether propranolol can manage blood sugar and fat levels during sleep in people with sleep apnea who stop using their CPAP machines. Propranolol works by blocking stress signals that increase these levels, potentially improving heart health and metabolism.

Research Team

Jonathan C Jun, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for people who have been diagnosed with Obstructive Sleep Apnea (OSA), are used to using CPAP machines, and can stop using them temporarily. They should not have other sleep disorders, certain heart conditions, severe lung diseases, or be taking conflicting medications.

Inclusion Criteria

If you have already taken part in the 'Metabolic Impact of Intermittent CPAP' study, you must have shown a more than 10% increase in nighttime fat or sugar levels during CPAP.

I use CPAP regularly but am willing to stop for this study.

I have severe obstructive sleep apnea.

Exclusion Criteria

I do not have serious heart conditions or uncontrolled high blood pressure.

I do not have sleep disorders, diabetes, or severe lung, kidney, or liver issues.

I am currently taking medication that may interact with the trial drug.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive propranolol or placebo during CPAP withdrawal nights to assess effects on nocturnal heart rate and vascular health

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Propranolol

Trial Overview The study aims to see if Propranolol helps lower blood sugar and fat levels during sleep in OSA patients compared to a placebo. It also looks at how it affects vascular function, sleep quality, and hemodynamics when CPAP is stopped.

Participant Groups

Group I: Propranolol Oral Tablet Active Control 2 Interventions

Subjects will be admitted to the clinical research unit. On the CPAP withdrawal nights, Propranolol LA (Inderal ® LA) 80 mg will be administered orally before sleep, at 6:30 PM, after dinner. Blood pressure will be measured before administration, at 10:30 PM, and 6:30 AM. They will sleep from 10:30 Pm to 6:30 AM. During sleep blood will be sampled from an indwelling IV for measurement of FFA, glucose, insulin, and triglycerides. This arm will be crossed-over to placebo 1 week later. This arm will is crossed-over with active drug 1 week before or after this study night.

Group II: Placebo Oral Tablet Placebo Group 2 Interventions

Subjects will be admitted to the clinical research unit. On the CPAP withdrawal nights, placebo of propranolol LA (Inderal ® LA) 80 mg will be administered orally at 6:30 PM, after dinner. Blood pressure will be measured before administration, at 10:30 PM, and 6:30 AM. They will sleep from 10:30 PM to 6:30 AM. During sleep blood will be sampled from an indwelling IV for measurement of FFA, glucose, insulin, and triglycerides. This arm will is crossed-over with active drug 1 week before or after this study night.

Propranolol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Inderex, a combination of bendrofluazide and sustained-release propranolol, was found to be more effective in lowering blood pressure compared to either medication alone in a study of 21 patients.

The study indicated that there were no significant differences in treatment responses across different age groups, suggesting that Inderex is a suitable option for a wide range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. Herrick, AL., Davis, JM., Weir, RJ.[2013]

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]

Inderectic, a combination of propranolol and bendrofluazide, significantly reduced blood pressure more effectively than either medication alone in a study of 21 hypertensive patients.

The study found that Inderectic was as effective as the same medications taken separately, with only minor side effects reported and no patients needing to withdraw from the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension. Jäättelä, A.[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]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

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]

References

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

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject. [2013]

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

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

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

Hypersomnolence with beta-adrenergic blockers. [2019]

4. Finland pubmed.ncbi.nlm.nih.gov

The fixed combination of propranolol and bendrofluazide in the treatment of hypertension. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. India pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. [2021]

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

Propranolol: long-term treatment in narcolepsy-cataplexy. [2019]

9. England pubmed.ncbi.nlm.nih.gov

beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Verapamil SR and propranolol LA: a comparison of efficacy and side effects in the treatment of mild to moderate hypertension. [2013]