Treatment of OSA Associated Hypertension With Alpha 2 Agonist or Diuretic

NCT02699125 | Completed Phase 4 Results

• 1 other identifier: guanhctz
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (1)

• 24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure

  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 Outcomes (1)

• Brachial Artery Flow Mediated Dilation

  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.

Study Arms (2)

Placebo, Guanfacine, Hydrochlorothyazide

EXPERIMENTAL

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; Drug: Hydrochlorothiazide

Placebo, Hydrochlorothyazide, Guanfacine

EXPERIMENTAL

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; Drug: Hydrochlorothiazide

Interventions

Guanfacine DRUG

Guanfacine 1mg for 2 weeks followed by guanfacine 2mg for 4 weeks.

Also known as: Tenex

Placebo, Guanfacine, Hydrochlorothyazide; Placebo, Hydrochlorothyazide, Guanfacine

Hydrochlorothiazide DRUG

Hydrochlorothiazide 12.5 mg for 2 weeks followed by hydrochlorothiazide 25 mg for 4 weeks

Also known as: Hydrodiuril

Placebo, Guanfacine, Hydrochlorothyazide; Placebo, Hydrochlorothyazide, Guanfacine

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ranging from 20 - 80 years
• 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
• Hypertension with blood pressures \> 140/90 but less than 180/105 mmHg.
• Apnea-hypopnea index above 10

You may not qualify if:

• 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.
• Women who have premenstrual syndrome, or those who are pregnant or capable of pregnancy and unwilling to use effective non-hormonal contraception
• Shift workers or have symptoms of narcolepsy, restless legs syndrome or insomnia, in order to minimize confounding effects of other sleep disorders
• Have apneas which are primarily central
• Have sleep fragmentation caused by syndromes such as chronic pain or movement disorders
• Have diseases such as asthma or chronic obstructive pulmonary disease that compromises respiration.
• Have known coronary or cerebral vascular disease, history of arrhythmias, cardiomyopathy, history of psychosis, current alcohol or drug abuse.
• Have any contraindications to any study materials, such as heart block.
• Have secondary hypertension
• Have creatinine levels above 2.5 mg %, more than 1+ proteinuria by dipstick, hematuria or electrolyte disorders.

Sponsors & Collaborators

• University of California, San Diego: lead

Related Publications (2)

• 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.

  PMID: 21326007 BACKGROUND

• Ziegler MG, Milic M, Dimsdale JE, Mills PJ. Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy. Clin Hypertens. 2024 Jun 1;30(1):14. doi: 10.1186/s40885-024-00272-x.

  PMID: 38822391 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Guanfacine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael G. Ziegler, M.D.
• Organization: University of California San Diego

mziegler@ucsd.edu

619 543 2885

Study Officials

• Michael G. Ziegler, M.D.

  UCSD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 4, 2016
• Study Start: January 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 4, 2020
• Results First Posted: December 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share