Propranolol for Sleep Apnea Therapy

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.

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