Treatment of OSA Associated Hypertension With Nebivolol or Hydrochlorothiazide
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Nebivolol; Hydrochlorothiazide
Intervention type(s): Drug; Drug
Intervention description(s): Nebivolol 5mg then nebivolol 10 mg; Hydrochlorothiazide 12.5 mg then hydrochlorothiazide 25 mg
Other intervention name(s): Bystolic; Hydrodiuril
Intervention MeSH terms: Hydrochlorothiazide; Nebivolol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment