Propranolol for Sleep Apnea Therapy (ProSAT)

August 14, 2024 updated by: Johns Hopkins University
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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 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.
Drug: Propranolol Oral Tablet
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
Other Names:
  • beta blocker
Drug: Placebo Oral Tablet
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)
Other Names:
  • 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 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.
Drug: Propranolol Oral Tablet
Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only)
Other Names:
  • beta blocker
Drug: Placebo Oral Tablet
Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only)
Other Names:
  • placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Nocturnal Heart Rate (Beats/Min, BPM)
Time Frame: 1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM
Average overnight heart rate (10:30 PM to 06:30 AM)
1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reactive Hyperemia Index (RHI)
Time Frame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Reactive Hyperemia Index (RHI) is measured by assessing the change in pulse wave amplitude in the brachial artery before and after a period of occlusion (usually 5 minutes). RHI is unitless as it reflects the ratio of pulse wave amplitude after : before occlusion. A high RHI indicates good endothelial function (values >1.67) and healthy vascular reactivity, while a low RHI (values <1.67) suggest endothelial dysfunction, which may be a risk factor for cardiovascular disease.
The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Systolic Blood Pressure (mmHg)
Time Frame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Measured in the morning (7 AM)
The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Diastolic Blood Pressure (mmHg)
Time Frame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Measured in the morning (7 AM)
The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
Augmentation Index (%)
Time Frame: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)
The Augmentation Index (AIx) is measured by analyzing the arterial pulse wave, which captures the pressure wave reflections in the arteries. A higher AIx indicates increased arterial stiffness and higher cardiovascular risk, while a lower AIx suggests more compliant, healthier arteries. AIx can theoretically range from negative values to over 100%, although clinical values usually are between -10% and +40%.
The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jonathan C Jun, MD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 15, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 5, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00113241
  • 1R03HL138068-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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