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

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ClinicalTrials.gov Identifier: NCT02699125
Recruitment Status : Unknown
Verified February 2016 by Michael G. Ziegler, University of California, San Diego.
Recruitment status was:  Active, not recruiting
First Posted : March 4, 2016
Last Update Posted : March 4, 2016
Sponsor:
Information provided by (Responsible Party):
Michael G. Ziegler, University of California, San Diego

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

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Drug: Guanfacine Drug: Hydrochlorothiazide Phase 4

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  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo Controlled Double Blinded Crossover Study of the Antihypertensive Efficacy of Guanfacine vs Hydrochlorothiazide in Obstructive Sleep Apnea (OSA) Associated Hypertension
Study Start Date : January 2015
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Placebo Comparator: guanfacine
Guanfacine 1mg for 2 weeks followed by guanfacine 2mg for 4 weeks.
Drug: Guanfacine
Guanfacine 1mg for 2 weeks followed by guanfacine 2mg for 4 weeks.
Other Name: Tenex

Active Comparator: Hydrochlorothiazide
Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks.
Drug: Hydrochlorothiazide
Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks
Other Name: Hydrodiuril




Primary Outcome Measures :
  1. Blood pressure [ Time Frame: at the end of 6 weeks of therapy ]
    24 hour ambulatory blood pressure


Secondary Outcome Measures :
  1. Flow mediated dilation [ Time Frame: at the end of 6 weeks of therapy ]
    Brachial artery dilation following occlusion



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02699125


Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Michael G. Ziegler, M.D. UCSD

Publications:
Responsible Party: Michael G. Ziegler, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02699125     History of Changes
Other Study ID Numbers: guanhctz
First Posted: March 4, 2016    Key Record Dates
Last Update Posted: March 4, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data may be shared with assurance of subject confidentiality

Additional relevant MeSH terms:
Hydrochlorothiazide
Hypertension
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Vascular Diseases
Cardiovascular Diseases
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Guanfacine
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents