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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether propranolol, a beta blocker typically used for heart issues, can assist people with obstructive sleep apnea (OSA) by lowering their heart rate at night when they stop using their CPAP machine. Researchers aim to determine if propranolol affects sleep quality, morning blood pressure, and blood vessel health. Individuals diagnosed with OSA, accustomed to using a CPAP, and willing to pause its use temporarily may be suitable candidates. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that propranolol is likely to be safe for humans?

Research has shown that propranolol, a beta blocker, is usually well-tolerated. Studies have found that propranolol effectively lowers heart rate, benefiting those with conditions like obstructive sleep apnea.

However, like any medication, it can cause side effects. Common side effects include fatigue, dizziness, or a slower heartbeat. Serious side effects are less common but can occur. Discuss any concerns with a healthcare provider.

Propranolol is already used for other health conditions, which provides some confidence about its safety. However, individual reactions can vary, so awareness of personal response to the medication is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for obstructive sleep apnea, like CPAP (Continuous Positive Airway Pressure) machines, focus on keeping the airway open during sleep. But propranolol, a beta-blocker, offers a different approach by potentially addressing some underlying physiological factors. Researchers are excited about propranolol because it could help manage sleep apnea by reducing sympathetic nervous system activity, which is often heightened in people with this condition. This means it might offer a more holistic solution compared to just managing airway obstruction. Additionally, propranolol is taken orally, which could be more convenient for some patients compared to using a CPAP machine every night.

What evidence suggests that propranolol might be an effective treatment for obstructive sleep apnea?

Research has shown that beta-blockers, such as propranolol, can lower blood pressure and heart rate. However, some evidence suggests these medications might increase heart-related risks in people with obstructive sleep apnea (OSA). Animal studies have shown mixed results regarding the effects of these drugs on heart rate during apnea episodes. While propranolol is known for controlling heart rate, its effects on sleep apnea remain unclear. This trial will compare propranolol with a placebo to better understand its safety and effectiveness for people with OSA. More research is needed to fully assess its safety and effectiveness for this population. ^{1 3 6 7 8}

Who Is on the Research Team?

Jonathan C Jun, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10432194/

Impact of beta-blockers on mortality and cardiovascular ...

Beta-blocker treatment was associated with an increased risk of CVD and a trend for an increased risk of mortality among patients with OSA.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03049306

NCT03049306 | Propranolol for Sleep Apnea Therapy

The primary objective of this study is to test whether a beta blocker, propranolol, lowers the overnight heart rate sleep in obstructive sleep apnea (OSA) ...

3.

ucl.ac.uk

ucl.ac.uk/life-sciences/news/2023/aug/new-study-finds-beta-blockers-increase-cardiovascular-risk-sleep-apnoea-patients

New study finds that beta-blockers increase cardiovascular ...

These findings suggest that beta-blocker use may pose an elevated risk to patients suffering from OSA, a condition that affects millions worldwide. Dr Kenneth ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4656106/

Effect of beta-blocker therapy on heart rate response in ...

Animal studies showed that intravenous infusion of propranolol had a diverse effect on periapneic bradycardias when compared to non-instrumented controls [22].

5.

mayoclinic.org

mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522

Beta blockers

Beta blockers are medicines that lower blood pressure. They also may be called beta-adrenergic blocking agents.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8109330/

The Antihypertensive Efficacy and Safety of a ...

Propranolol CR significantly reduced mean morning heart rate in all groups compared with placebo (Figure 3). Similar significant decreases were seen when heart ...

7.

goodrx.com

goodrx.com/propranolol/propranolol-side-effects?srsltid=AfmBOop5ZyITETeuxvkFsa3TqCA77IXWUEGTvfSRsD41rpTkNzZrNL3t

10 Propranolol Side Effects You Should Know About

Read on to learn the common and rare side effects for propranolol, and when to reach out to your healthcare team for further guidance.

8.

elsevier.health

elsevier.health/en-US/preview/propranolol

Propranolol

Initially, 10 to 20 mg PO 2 to 4 times per day, then increase at 3 to 7 day intervals up to 160 to 320 mg/day, given in 2 to 4 divided doses ...