Propranolol for Sleep Apnea Therapy

Obstructive Sleep Apnea Clinical Trial

— ProSAT  

Official title:

Propranolol for Sleep Apnea Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03049306
• Other study ID #: IRB00113241
• Secondary ID: 1R03HL138068-01
• Status: Completed
• Phase: Phase 2
• Start date: February 15, 2017
• Est. completion date: May 1, 2024

Study information

• Verified date: May 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective in this study is to test whether propranolol lowers glucose and free fatty acid levels during sleep in obstructive sleep apnea (OSA), and preserves vascular function (EndoPAT) versus placebo. The secondary objective is to test whether propranolol influences sleep quality, architecture, and hemodynamics in OSA. OSA will be elicited by temporarily discontinuing CPAP therapy in patients with a history OSA accustomed to CPAP therapy (CPAP withdrawal).

Description:

Free fatty acids and glucose elevations occur during the night in obstructive sleep apnea (OSA) patients, and these elevations may be responsible for adverse cardio-metabolic consequences of OSA. The sympathetic nervous system is well known to mediate adipose tissue lipolysis as well as "stress hyperglycemia". Thus, investigators may be able to mitigate these nocturnal metabolic changes with beta adrenergic blockade. 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 compare nocturnal metabolic profiles and hemodynamics on/off propranolol in the setting of CPAP withdrawal.

This study examines whether propranolol prevents changes in blood pressure, heart rate, and blood flow during sleep during CPAP withdrawal. Propranolol or placebo is given during the CPAP withdrawal visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Propranolol Oral Tablet
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
• Placebo Oral Tablet
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocturnal heart rate	Average heart rate (comparing propranolol to placebo)	During each of two sleep studies.
Secondary	Reactive Hyperemia Index, RHI	Measured in the morning (7 AM) after each of the two sleep studies	Measured twice within 1 month
Secondary	Systolic Blood pressure (mmHg)	Measured in the morning (7 AM) after each sleep study	Measured twice within 1 month
Secondary	Diastolic Blood pressure (mmHg)	Measured in the morning (7 AM) after each of the two sleep studies	Measured twice within 1 month
Secondary	Augmentation index (%)	Measured in the morning (7 AM) after each of the two sleep studies	Measured twice within 1 month