Treatment of OSA Associated Hypertension With Alpha 2 Agonist or Diuretic (guanhctz)

November 10, 2020 updated by: Michael G. Ziegler, University of California, San Diego

A Placebo Controlled Double Blinded Crossover Study of the Antihypertensive Efficacy of Guanfacine vs Hydrochlorothiazide in Obstructive Sleep Apnea (OSA) Associated Hypertension

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 guanfacine or hydrochlorothiazide (HCTZ) for 6 weeks after 2 weeks of placebo. The blood pressure response will be evaluated by 24 hour monitoring.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a blinded crossover study measuring the antihypertensive efficacy of guanfacine 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 guanfacine 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 Guanfacine 1mg will be taken daily at bedtime for 2 weeks and then as a dose of 2 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, such as excessive somnolence, drowsiness, or depression, 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.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 4

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

Ages Eligible for Study

18 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients ranging from 20 - 80 years
  2. Body mass index (BMI) of 20-38 to include the typical obese OSA patients and avoid the practical difficulties in blood drawing from the massively obese
  3. Hypertension with blood pressures > 140/90 but less than 180/105 mmHg.
  4. Apnea-hypopnea index above 10

Exclusion Criteria:

  1. Receiving medications other than anti-hypertensives known to influence the sympathetic nervous system, sleep medicines (including heavy alcohol use) or drugs with adverse interactions with study medication.
  2. Women who have premenstrual syndrome, or those who are pregnant or capable of pregnancy and unwilling to use effective non-hormonal contraception
  3. Shift workers or have symptoms of narcolepsy, restless legs syndrome or insomnia, in order to minimize confounding effects of other sleep disorders
  4. Have apneas which are primarily central
  5. Have sleep fragmentation caused by syndromes such as chronic pain or movement disorders
  6. Have diseases such as asthma or chronic obstructive pulmonary disease that compromises respiration.
  7. Have known coronary or cerebral vascular disease, history of arrhythmias, cardiomyopathy, history of psychosis, current alcohol or drug abuse.
  8. Have any contraindications to any study materials, such as heart block.
  9. Have secondary hypertension
  10. Have creatinine levels above 2.5 mg %, more than 1+ proteinuria by dipstick, hematuria or electrolyte disorders.

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo, Guanfacine, Hydrochlorothyazide
Sequence: Placebo, Then Guanfacine1 mg for 2 weeks followed by guanfacine 2 mg for 4 weeks, Then Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks.
Drug: Guanfacine
Guanfacine 1mg for 2 weeks followed by guanfacine 2mg for 4 weeks.
Other Names:
  • Tenex
Drug: Hydrochlorothiazide
Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks
Other Names:
  • Hydrodiuril
Experimental: Placebo, Hydrochlorothyazide, Guanfacine
Sequence: Placebo, Then Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks, Then Guanfacine1 mg for 2 weeks followed by guanfacine 2 mg for 4 weeks.
Drug: Guanfacine
Guanfacine 1mg for 2 weeks followed by guanfacine 2mg for 4 weeks.
Other Names:
  • Tenex
Drug: Hydrochlorothiazide
Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks
Other Names:
  • Hydrodiuril

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure
Time Frame: At the end of 2 weeks of placebo therapy, at the end of 6 weeks of guanfacine therapy and at the end of 6 weeks of hydrochlorothiazide therapy.
The primary outcome measure is ambulatory systolic and diastolic blood pressure recorded once every 15 minutes during the day and once every 30 minutes during the sleep. The Outcome Measure Data Table present primary outcome as "24-h", "Wake" and "Sleep" Period Systolic and Diastolic Blood Pressure after each of the following three interventions: Placebo, Guanfacine and Hydrochlorothiazide.
At the end of 2 weeks of placebo therapy, at the end of 6 weeks of guanfacine therapy and at the end of 6 weeks of hydrochlorothiazide therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brachial Artery Flow Mediated Dilation
Time Frame: At the end of 2 weeks of placebo therapy, at the end of 6 weeks of guanfacine therapy and at the end of 6 weeks of hydrochlorothiazide therapy.
Brachial Artery Flow Mediated Dilation is upper arm brachial artery dilation during the 3 minutes forearm reactive hyperemia following the release of the 5-minute forearm cuff occlusion.
At the end of 2 weeks of placebo therapy, at the end of 6 weeks of guanfacine therapy and at the end of 6 weeks of hydrochlorothiazide therapy.

Collaborators and Investigators

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

Sponsor

University of California, San Diego

Investigators

  • Principal Investigator: Michael G. Ziegler, M.D., UCSD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

January 1, 2015

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

February 26, 2016

First Submitted That Met QC Criteria

February 29, 2016

First Posted (Estimate)

March 4, 2016

Study Record Updates

Last Update Posted (Actual)

December 4, 2020

Last Update Submitted That Met QC Criteria

November 10, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • guanhctz

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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