Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Patients who have obstructive sleep apnea (OSA) frequently stop breathing while they sleep. They often develop high blood pressure. We are not sure what drug is best to treat the high blood pressure. This study will give the patients nebivolol or hydrochlorothiazide (HCTZ) for 6 weeks after 2 weeks of placebo. The blood pressure response will be evaluated by 24 hour monitoring.
This is a blinded crossover study measuring the antihypertensive efficacy of nebivolol vs HCTZ in up to 34 subjects. Subjects with an apnea-hypopnea index (AHI) > 10 and hypertension can enter the study. Hypertension is defined as a systolic blood pressure (SBP) > 140 or a diastolic blood pressure (DBP) > 90 on the average of three seated blood pressure measurements or a history of medical therapy for hypertension. Subjects who have tried and abandoned continuous positive airway pressure (CPAP) therapy for sleep apnea are eligible for this study. All others will be advised that CPAP is preferred treatment for sleep apnea and are eligible only if they decline CPAP or use it for too short a time at night to be effective.
Then patients will have their antihypertensive drugs tapered off and receive single blind placebo for two weeks. After that, all subjects receive nebivolol or HCTZ for six weeks with a full evaluation at that time. Subjects are crossed over to HCTZ 12.5 mg for 2 weeks followed by HCTZ 25 mg for 4 more weeks. Nebivolol 5 mg will be taken daily at bedtime for 2 weeks and then as a dose of 10 mg for the remaining 4 weeks. Subjects will receive a telephone call at the time of increased dosage as a reminder. Blood, urine and 24-hour blood pressure measurements, hemodynamic measurements, questionnaires and drug accountability are measured in the same manner toward at the the end of placebo and each drug treatment. The entire study will take 14 weeks, although each study period may be lengthened by one week if necessary for the convenience of the subject's personal schedule.
Patients will provide blood pressure readings from their home monitor or in clinic and will not have the dose increased if they have systolic blood pressure below 105 mm Hg or side effects suggesting that an increased dose might worsen side effects
At the end of each treatment period, subjects will undergo noninvasive hemodynamic testing. Ultrasound will be used to measure aortic diameter and blood velocity in the ascending aorta in order to better estimate cardiac output. Then, finger plethysmography will be used to acquire beat-to-beat finger blood pressure and pulse rate. Beat-to-beat derived hemodynamic variables will be calculated by a model flow algorithm (e.g. brachial artery flow, stroke volume, cardiac output, ejection time, blood pressure rate of change, peripheral resistance). Applanation tonometry will be used to obtain pulse wave velocity and central arterial pressure. ECG will be recorded with standard ECG leads to determine heart rate variability in both time and frequency domains. Spontaneous baroreflex will be determined from beat-to-beat changes in blood pressure and pulse pressure interval. Forearm reactive hyperemia will be used to quantify endothelial dysfunction during 4 minutes of post-ischemic change. Subjects will then complete an Epworth Sleepiness Scale questionnaire (ESS) and a Functional Outcomes of Sleep Questionnaire (FOSQ) to find whether they are drowsy in the daytime and if they feel that they are compromised by not having adequate rest. Any adverse event will be recorded. They are asked about any concurrent medication over the prior period, including prescription medication, over the counter medication, and caffeine intake. Medication compliance is evaluated by pill count. Those who fail to return their pill bottle are requested to bring it in. Finally, a 24-hour ambulatory blood pressure monitor (ABPM) will be attached to automatically collect blood pressure and heart rate values every 15 minutes during the wake period and every 30 minutes during the sleep period.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo, Nebivolol, Hydrochlorothyazide | Experimental | Sequence: Placebo, Then Nebivolol 5mg for 2 weeks followed by nebivolol 10 mg for 4 weeks,Then Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks. |
|
| Placebo, Hydrochlorothyazide, Nebivolol | Experimental | Sequence: Placebo, Then Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks, Then Nebivolol 5mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nebivolol | Drug | Nebivolol 5mg then nebivolol 10 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure | 24-h Systolic Blood Pressure is the average of all 24-h Ambulatory Systolic Blood Pressure recordings. The Wake Period Systolic Blood Pressure is the average of all Systolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Systolic Blood pressure is the average of all Systolic Blood Pressures recorded every 30 minutes during the sleep period. 24-h Diastolic Blood Pressure is the average of all 24-h Ambulatory Diastolic Blood Pressure recordings. The Wake Period Diastolic Blood Pressure is the average of all Diastolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Diastolic Blood pressure is the average of all Diastolic Blood Pressures recorded every 30 minutes during the sleep period. | At the end of 2 weeks of placebo therapy, at the end of 6 weeks of Nebivolol therapy and at the end of 6 weeks of hydrochlorothiazide therapy. |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Michael G. Ziegler, M.D. | Professor of Medicine | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21326007 | Background | Ziegler MG, Milic M, Sun P. Antihypertensive therapy for patients with obstructive sleep apnea. Curr Opin Nephrol Hypertens. 2011 Jan;20(1):50-5. doi: 10.1097/MNH.0b013e3283402eb5. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
41 of 405 participants were randomized. Of those not randomized, 364 did not meet inclusion criteria
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo, Then Nebivolol, Then Hydrochlorothyazide | The participants first received Placebo for 2 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. |
| FG001 | Placebo, Then Hydrochlorothiazide, Then Nebivolol | The participants first received Placebo for 2 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Placebo (2 Weeks). |
| |||||||||||||
| First Intervention (6 Weeks). |
| |||||||||||||
| Second Intervention (6 Weeks). |
|
In the study arm 1 ("Placebo, Then Nebivolol, Then Hydrochlorothiazide"): 21 participant first received baseline Placebo for 2 weeks. In the study arm 2 ("Placebo, Then Hydrochlorothiazide, Then Nebivolol" ): 20 participants first received baseline Placebo for 2 weeks.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo, Then Nebivolol, Then Hydrochlorothiazide | The participants first received Placebo for 2 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | 24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure | 24-h Systolic Blood Pressure is the average of all 24-h Ambulatory Systolic Blood Pressure recordings. The Wake Period Systolic Blood Pressure is the average of all Systolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Systolic Blood pressure is the average of all Systolic Blood Pressures recorded every 30 minutes during the sleep period. 24-h Diastolic Blood Pressure is the average of all 24-h Ambulatory Diastolic Blood Pressure recordings. The Wake Period Diastolic Blood Pressure is the average of all Diastolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Diastolic Blood pressure is the average of all Diastolic Blood Pressures recorded every 30 minutes during the sleep period. | The overall Number of Analyzed Participants for primary outcome (27) differs from the Overall Number of Placebo (baseline) Participants (41) because 14 participants were excluded from the analysis due to either low quality of acquired data or due to missing data. Data Analysis was performed for the same 27 participants and for the each test period. | Posted | Mean | Standard Error | mmHg | At the end of 2 weeks of placebo therapy, at the end of 6 weeks of Nebivolol therapy and at the end of 6 weeks of hydrochlorothiazide therapy. |
16 weeks.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo, Then Nebivolol, Then Hydrochlorothyazide | Participants first received Placebo for 2 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael G. Ziegler, M.D. | University of California San Diego | 619 543 2885 | mziegler@ucsd.edu |
Not provided
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068577 | Nebivolol |
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Hydrochlorothiazide | Drug | Hydrochlorothiazide 12.5 mg then hydrochlorothiazide 25 mg |
|
|
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
|
| Placebo, Then Hydrochlorothiazide, Then Nebivolol |
The participants first received Placebo for 2 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 24-h Ambulatory Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 0 |
| 21 |
| EG001 | Placebo, Then Hydrochlorothyazide, Then Nebivolol | Participants first received Placebo for 2 weeks. They then received hydrochlorothyazide 12.5 mg for 2 weeks followed by hydrochlorothyazide 25 mg for 4 weeks. They then received nebivolol 5 mg for 2 weeks followed by nebivolol 10 mg for 4 weeks. | 0 | 20 | 0 | 20 | 0 | 20 |
Not provided
Not provided
Not provided
| D000588 |
| Amines |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D049971 | Thiazides |