Propranolol for Sleep Apnea Therapy

NCT ID: NCT03049306

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-15
• Study Completion Date: 2024-05-01

Brief Summary

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) during CPAP withdrawal. The secondary objectives are to test whether propranolol influences sleep architecture, morning blood pressure, and vascular function including reactive hyperemia index (RHI) and a marker of arterial stiffness, augmentation index (AIX).

Detailed Description

The overnight heart rate is increased in patients with obstructive sleep apnea (OSA), reflecting excessive sympathetic nervous system activity which may lead to long-term adverse cardiovascular consequences. Propranolol is a non-selective beta blocker that is used for a variety of indications including hypertension and anxiety. In this study investigators will administer propranolol or placebo to patients with OSA before sleep. Investigators will examine the effect of drug on nocturnal heart rate, morning blood pressure, and vascular health outcomes

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo Oral Tablet

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.

Group Type: PLACEBO_COMPARATOR

Propranolol Oral Tablet

Intervention Type: DRUG

Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)

Placebo Oral Tablet

Intervention Type: DRUG

Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)

Propranolol Oral Tablet

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 Type: ACTIVE_COMPARATOR

Propranolol Oral Tablet

Intervention Type: DRUG

Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)

Placebo Oral Tablet

Intervention Type: DRUG

Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)

Interventions

Propranolol Oral Tablet

Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)

Intervention Type: DRUG

Placebo Oral Tablet

Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)

Intervention Type: DRUG

Other Intervention Names

beta blocker; placebo

Eligibility Criteria

Inclusion Criteria

• History of OSA (AHI>20, >50% events obstructive)
• Accustomed to CPAP use, and willing to discontinue CPAP temporarily for the study.
• If the participant has already completed "Metabolic Impact of Intermittent CPAP" (NA_00086830), they must have exhibited a >10% increase in nocturnal FFA or glucose during CPAP

Exclusion Criteria

• Cardiovascular risks

• Decompensated congestive heart failure
• Atrial fibrillation, sick sinus syndrome, 2nd or 3rd degree heart block, pacemaker implantation, Wolff-Parkinson-White Syndrome (if not known, will check on a screening EKG)
• Uncontrolled hypertension > 170/110
• History of postural hypotension.
• Resting systolic pressure <90 or heart rate < 50 on screening visit
• Drug interactions - currently taking any of the following drugs. (Subjects on these medications are excluded from participation and will not have the drug in question discontinued for the purposes of participation in the study. )

• Calcium channel blockers that reduce heart rate (diltiazem, verapamil, fendiline, gallopamil)
• Sympatholytic drugs: any other beta blocker; clonidine, terazosin or doxazosin; reserpine
• Anti-arrhythmic drugs: (e.g. amiodarone, sotalol, digoxin, quinidine, lidocaine, propafenone)
• Coumadin (propranolol may prolong INR)
• Drugs that Inhibit CYP2D6, CYP1A2, or CYP2C19: amiodarone, ciprofloxacin, cimetidine, delavirdine, fluconazole, fluoxetine, fluvoxamine, imipramine, isoniazid, paroxetine, quinidine, ritonavir, rizatriptan, teniposide, theophylline, tolbutamide, zileuton, zolmitriptan
• Drugs that increase hepatic metabolism of propranolol: rifampin, ethanol, phenytoin, and phenobarbital
• Neuroleptics/anxiolytics: (thioridazine, chlorpromazine - may increase propranolol level), haloperidol, valium
• Illicit drugs such as cocaine or amphetamines.
• Other medical conditions

• Sleep disorder other than OSA, including: restless leg syndrome, parasomnia, or narcolepsy.
• Shift work or circadian rhythm disorder that is expected to prevent good sleep as scheduled in the protocol
• Insulin-dependent diabetes mellitus
• Myasthenia gravis
• Pheochromocytoma
• Uncontrolled bronchospastic lung disease such as asthma or chronic obstructive pulmonary disease (COPD)
• Current smoking
• Chronic renal or liver failure
• Known pregnancy, by urine testing in women of child-bearing age; nursing mothers
• Known hypersensitivity to any beta blocker
• History of falling asleep while driving, near miss
• High risk occupation (pilot, commercial driver) Hemoglobin < 10 g/dL on point of care screening

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan C Jun, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R03HL138068-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00113241

Identifier Type: -

Identifier Source: org_study_id