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| ID | Type | Description | Link |
|---|---|---|---|
| 1R03HL138068-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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).
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Oral Tablet | Placebo Comparator | 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. |
|
| Propranolol Oral Tablet | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol Oral Tablet | Drug | Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Nocturnal Heart Rate (Beats/Min, BPM) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Reactive Hyperemia Index (RHI) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
Cardiovascular risks
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. )
Other medical conditions
History of falling asleep while driving, near miss
High risk occupation (pilot, commercial driver) Hemoglobin < 10 g/dL on point of care screening
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan C Jun, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Bayview Medical Center | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41811641 | Derived | Pham LV, Duan D, Badami V, Perin J, Potocki M, Polotsky VY, Jun JC. Propranolol mitigates sleep apnea-related cardiac responses during CPAP withdrawal: a randomized placebo-controlled cross-over clinical study. Sleep Breath. 2026 Mar 11;30(1):88. doi: 10.1007/s11325-026-03645-8. |
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24 participants signed a consent form. 1 subject was lost to follow up after consent, leaving 23 participants who were randomized to placebo first (n=11) or propranolol first (n=12).
Patients with a history of obstructive sleep apnea (OSA) who were accustomed to continuous positive airway pressure (CPAP) use were enrolled from the Johns Hopkins Sleep Disorders Center. Patients with arrhythmias or taking beta blockers were excluded, among other criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo First, Then Propranolol | This is a crossover study comparing placebo to propranolol taken before sleep prior to CPAP withdrawal. This arm received placebo during the first intervention and propranolol during the second intervention. |
| FG001 | Propranolol First, Then Placebo | This is a crossover study comparing placebo to propranolol taken before sleep prior to CPAP withdrawal. This arm received propranolol during the first intervention and placebo during the second intervention. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Night) |
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| ||||||||||||||||||
| Second Intervention (1 Night) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo First, Then Propranolol | This is a crossover study comparing placebo to propranolol taken before sleep prior to CPAP withdrawal. This arm received placebo during the first intervention and propranolol during the second intervention. |
| BG001 | Propranolol First, Then Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Nocturnal Heart Rate (Beats/Min, BPM) | Average overnight heart rate (10:30 PM to 06:30 AM) | Posted | Mean | Standard Deviation | BPM | 1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM |
|
Up to 3 weeks
We screened for the presence of:
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Propranolol Oral Tablet: Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only) Placebo Oral Tablet: Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Jun | Johns Hopkins University School of Medicine | 410-550-0115 | jjun2@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 17, 2021 | Jul 8, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 25, 2023 | Jul 8, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 6, 2022 | Jul 8, 2024 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D000319 | Adrenergic beta-Antagonists |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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|
| Placebo Oral Tablet | Drug | Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only) |
|
|
| The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention) |
| Systolic Blood Pressure (mmHg) | 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) | 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 (%) | 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) |
| NOT COMPLETED |
|
This is a crossover study comparing placebo to propranolol taken before sleep prior to CPAP withdrawal. This arm received propranolol during the first intervention and placebo during the second intervention. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | 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. Propranolol Oral Tablet: Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only) Placebo Oral Tablet: Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only) |
|
|
| Secondary | Reactive Hyperemia Index (RHI) | 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. | Posted | Mean | Standard Deviation | Ratio | The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention) |
|
|
|
| Secondary | Systolic Blood Pressure (mmHg) | Measured in the morning (7 AM) | Posted | Mean | Standard Deviation | mmHg | The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention) |
|
|
|
| Secondary | Diastolic Blood Pressure (mmHg) | Measured in the morning (7 AM) | Posted | Mean | Standard Deviation | mmHg | The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention) |
|
|
|
| Secondary | Augmentation Index (%) | 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%. | Posted | Mean | Standard Deviation | Percentage of arterial pulse pressure | The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention) |
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 0 |
| 21 |
| EG001 | 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. Propranolol Oral Tablet: Patients will receive Propranolol LA 80 mg PO at 7 PM before sleep (on CPAP withdrawal nights only) Placebo Oral Tablet: Patients will receive Placebo tablet at 7 PM before sleep (on CPAP withdrawal nights only) | 0 | 21 | 0 | 21 | 0 | 21 |
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| D020919 |
| Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |