Clinical trial NCT03049306: Propranolol for Sleep Apnea Therapy
Official title: Propranolol for Sleep Apnea Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Keywords: Obstructive sleep apnea
CPAP
Propranolol
Metabolism
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-02-10
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Nocturnal Heart Rate (Beats/Min, BPM)
timeFrame: 1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM
Secondary outcomes:
measure: Reactive Hyperemia Index (RHI)
timeFrame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
measure: Systolic Blood Pressure (mmHg)
timeFrame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
measure: Diastolic Blood Pressure (mmHg)
timeFrame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
measure: Augmentation Index (%)
timeFrame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jonathan C Jun, MD
role: PRINCIPAL_INVESTIGATOR
References: