Propranolol for Sleep Apnea Therapy (ProSAT)

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Obstructive Sleep Apnea

Treatments: Drug: Propranolol Oral Tablet; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03049306

IRB00113241

1R03HL138068-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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

Enrollment: 24 patients

Sex: All

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24 participants in 2 patient groups, including a placebo group

Placebo Oral Tablet

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo Oral Tablet

Drug: Propranolol Oral Tablet

Propranolol Oral Tablet

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo Oral Tablet

Drug: Propranolol Oral Tablet