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Propranolol for Sleep Apnea Therapy (ProSAT)

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ClinicalTrials.gov Identifier: NCT03049306
Recruitment Status : Enrolling by invitation
First Posted : February 10, 2017
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Johns Hopkins University

Brief 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).

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Drug: Propranolol Oral Tablet Drug: Placebo Oral Tablet Device: CPAP Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Propranolol for Sleep Apnea Therapy
Actual Study Start Date : February 15, 2017
Estimated Primary Completion Date : January 1, 2023
Estimated Study Completion Date : January 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Placebo Comparator: Placebo Oral Tablet
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 7 PM, after dinner. Blood pressure will be measured before administration, at 11 PM, and 7 AM. They will sleep from 11 Pm to 7 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
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
Other Name: beta blocker

Drug: Placebo Oral Tablet
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)
Other Name: placebo

Active Comparator: Propranolol Oral Tablet
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 7 PM, after dinner. Blood pressure will be measured before administration, at 11 PM, and 7 AM. They will sleep from 11 Pm to 7 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
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
Other Name: beta blocker

Drug: Placebo Oral Tablet
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)
Other Name: placebo

Active Comparator: CPAP
Subjects will be admitted to the clinical research unit. They will sleep wearing CPAP according to their usual home settings. Blood pressure will be measured before administration, at 11 PM, and 7 AM. They will sleep from 11 Pm to 7 AM. During sleep blood will be sampled from an indwelling IV for measurement of FFA, glucose, insulin, and triglycerides.
Device: CPAP
Patients will sleep in the lab wearing CPAP




Primary Outcome Measures :
  1. Free fatty acid (FFA, mmol/L) [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.


Secondary Outcome Measures :
  1. Oral Glucose Tolerance Test (OGTT) [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.

  2. Reactive hyperemia Index [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Measured in the morning after each sleep study (around 7 :30 am), using Itamar EndoPAT device. The data will be presented upon study completion.

  3. Blood pressure, mmHg [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.

  4. Heart rate [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.

  5. Sleep quality and side effect questionnaire [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Questionnaire including questions about sleep quality and possible side effects from study drug on 3 separate visits.

  6. Glucose (mg/dl) [ Time Frame: 3 nights, <3 weeks apart completed within 1 month ]
    Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03049306


Locations
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United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Jonathan C Jun, MD Johns Hopkins University

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03049306     History of Changes
Other Study ID Numbers: IRB00113241
1R03HL138068-01 ( U.S. NIH Grant/Contract )
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins University:
Obstructive sleep apnea
CPAP
Propranolol
Metabolism
Additional relevant MeSH terms:
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Propranolol
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents