Trial Outcomes & Findings for Propranolol for Sleep Apnea Therapy (NCT NCT03049306)
NCT ID: NCT03049306
Last Updated: 2024-09-05
Results Overview
Average overnight heart rate (10:30 PM to 06:30 AM)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AM
Results posted on
2024-09-05
Participant Flow
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.
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).
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
First Intervention (1 Night)
STARTED
|
11
|
12
|
|
First Intervention (1 Night)
COMPLETED
|
10
|
11
|
|
First Intervention (1 Night)
NOT COMPLETED
|
1
|
1
|
|
Second Intervention (1 Night)
STARTED
|
10
|
11
|
|
Second Intervention (1 Night)
COMPLETED
|
10
|
11
|
|
Second Intervention (1 Night)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
First Intervention (1 Night)
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Propranolol for Sleep Apnea Therapy
Baseline characteristics by cohort
| Measure |
Placebo First, Then Propranolol
n=11 Participants
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.
|
Propranolol First, Then Placebo
n=12 Participants
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.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 9 • n=5 Participants
|
52 years
STANDARD_DEVIATION 13 • n=7 Participants
|
51 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 Night (approximately 4 hours post administration for each intervention), from 10:30 PM to 06:30 AMAverage overnight heart rate (10:30 PM to 06:30 AM)
Outcome measures
| Measure |
Placebo Oral Tablet
n=21 Participants
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 free fatty acids (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)
|
Propranolol Oral Tablet
n=21 Participants
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)
|
|---|---|---|
|
Nocturnal Heart Rate (Beats/Min, BPM)
|
64.1 BPM
Standard Deviation 5.1
|
60.2 BPM
Standard Deviation 4.4
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Placebo Oral Tablet
n=21 Participants
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 free fatty acids (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)
|
Propranolol Oral Tablet
n=21 Participants
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)
|
|---|---|---|
|
Reactive Hyperemia Index (RHI)
|
2.04 Ratio
Standard Deviation 0.55
|
2.11 Ratio
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)Measured in the morning (7 AM)
Outcome measures
| Measure |
Placebo Oral Tablet
n=21 Participants
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 free fatty acids (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)
|
Propranolol Oral Tablet
n=21 Participants
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)
|
|---|---|---|
|
Systolic Blood Pressure (mmHg)
|
131 mmHg
Standard Deviation 14
|
125 mmHg
Standard Deviation 15
|
SECONDARY outcome
Timeframe: The morning after each intervention at 7:00 AM (approximately 11.5 hours post administration for each intervention)Measured in the morning (7 AM)
Outcome measures
| Measure |
Placebo Oral Tablet
n=21 Participants
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 free fatty acids (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)
|
Propranolol Oral Tablet
n=21 Participants
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)
|
|---|---|---|
|
Diastolic Blood Pressure (mmHg)
|
80 mmHg
Standard Deviation 9
|
76 mmHg
Standard Deviation 11
|
SECONDARY outcome
Timeframe: 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%.
Outcome measures
| Measure |
Placebo Oral Tablet
n=21 Participants
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 free fatty acids (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)
|
Propranolol Oral Tablet
n=21 Participants
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)
|
|---|---|---|
|
Augmentation Index (%)
|
14 Percentage of arterial pulse pressure
Standard Deviation 19
|
21 Percentage of arterial pulse pressure
Standard Deviation 18
|
Adverse Events
Placebo Oral Tablet
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Propranolol Oral Tablet
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Jonathan Jun
Johns Hopkins University School of Medicine
Phone: 410-550-0115
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place