Propranolol for Sleep Apnea Therapy

NCT03049306 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: IRB001132411R03HL138068-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive sleep apnea; CPAP; Propranolol; Metabolism

Outcome Measures

Primary Outcomes (1)

• Nocturnal Heart Rate (Beats/Min, BPM)

  Average overnight heart rate (10:30 PM to 06:30 AM)

  1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM

Secondary Outcomes (4)

• Reactive Hyperemia Index (RHI)

  The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)

• Systolic Blood Pressure (mmHg)

  The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)

• Diastolic Blood Pressure (mmHg)

  The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)

• Augmentation Index (%)

  The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)

Study Arms (2)

Placebo Oral Tablet

PLACEBO COMPARATOR

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.

Drug: Propranolol Oral Tablet; Drug: Placebo Oral Tablet

Propranolol Oral Tablet

ACTIVE COMPARATOR

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.

Drug: Propranolol Oral Tablet; Drug: Placebo Oral Tablet

Interventions

Propranolol Oral Tablet DRUG

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

Also known as: beta blocker

Placebo Oral Tablet; Propranolol Oral Tablet

Placebo Oral Tablet DRUG

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

Also known as: placebo

Placebo Oral Tablet; Propranolol Oral Tablet

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Propranolol; Adrenergic beta-Antagonists

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Results Point of Contact

• Title: Jonathan Jun
• Organization: Johns Hopkins University School of Medicine

jjun2@jhmi.edu

410-550-0115

Study Officials

• Jonathan C Jun, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: February 10, 2017
• Study Start: February 15, 2017
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: September 5, 2024
• Results First Posted: September 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)