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Propranolol for Sleep Apnea Therapy (ProSAT)

Primary Purpose

Obstructive Sleep Apnea

Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Propranolol Oral Tablet
Placebo Oral Tablet
CPAP
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea focused on measuring Obstructive sleep apnea, CPAP, Propranolol, Metabolism

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Johns Hopkins Bayview Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo Oral Tablet

Propranolol Oral Tablet

CPAP

Arm 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 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. This visit is part of both the PROSAT 1.0 and PROSAT 2.0 study.

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. This visit is part of both the PROSAT 1.0 and PROSAT 2.0 study.

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. This visit part of the PROSAT 1.0 study.

Outcomes

Primary Outcome Measures

Free fatty acid (FFA, mmol/L)
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.

Secondary Outcome Measures

Oral Glucose Tolerance Test (OGTT)
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.
Reactive hyperemia Index
Measured in the morning after each sleep study (around 7 :30 am), using Itamar EndoPAT device. The data will be presented upon study completion.
Blood pressure, mmHg
Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.
Heart rate
Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.
Sleep quality and side effect questionnaire
Questionnaire including questions about sleep quality and possible side effects from study drug on 3 separate visits.
Glucose (mg/dl)
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.

Full Information

First Posted
December 6, 2016
Last Updated
August 28, 2023
Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03049306
Brief Title
Propranolol for Sleep Apnea Therapy
Acronym
ProSAT
Official Title
Propranolol for Sleep Apnea Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
February 15, 2017 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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).
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. This study involves 3 visits, one visit on CPAP and the other 2 visits after CPAP withdrawal. Propranolol or placebo is given during the CPAP withdrawal visits. A sub-study called "PROSAT 2" examines whether propranolol prevents changes in blood pressure, heart rate, and blood flow during sleep. PROSAT 2 involves only 2 visits, both after CPAP withdrawal. Propranolol or placebo is given during the CPAP withdrawal visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Obstructive sleep apnea, CPAP, Propranolol, Metabolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo Oral Tablet
Arm Type
Placebo Comparator
Arm 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 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. This visit is part of both the PROSAT 1.0 and PROSAT 2.0 study.
Arm Title
Propranolol Oral Tablet
Arm Type
Active Comparator
Arm 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 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. This visit is part of both the PROSAT 1.0 and PROSAT 2.0 study.
Arm Title
CPAP
Arm Type
Active Comparator
Arm Description
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. This visit part of the PROSAT 1.0 study.
Intervention Type
Drug
Intervention Name(s)
Propranolol Oral Tablet
Other Intervention Name(s)
beta blocker
Intervention Description
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
placebo
Intervention Description
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)
Intervention Type
Device
Intervention Name(s)
CPAP
Intervention Description
Patients will sleep in the lab wearing CPAP
Primary Outcome Measure Information:
Title
Free fatty acid (FFA, mmol/L)
Description
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Secondary Outcome Measure Information:
Title
Oral Glucose Tolerance Test (OGTT)
Description
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Title
Reactive hyperemia Index
Description
Measured in the morning after each sleep study (around 7 :30 am), using Itamar EndoPAT device. The data will be presented upon study completion.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Title
Blood pressure, mmHg
Description
Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Title
Heart rate
Description
Measured before drug administration (7 PM), before sleep (9 PM, 11 PM) and in the morning (7 AM) on 3 separate visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Title
Sleep quality and side effect questionnaire
Description
Questionnaire including questions about sleep quality and possible side effects from study drug on 3 separate visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month
Title
Glucose (mg/dl)
Description
Serial blood samples taken before, during, and after sleep, 27 time points per night on 3 separate study visits.
Time Frame
3 nights, <3 weeks apart completed within 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan C Jun, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Propranolol for Sleep Apnea Therapy

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