Study of Cardiovascular Disease and Obstructive Sleep Apnea

NCT ID: NCT01637623

Last Updated: 2020-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2015-06-30

Brief Summary

The purpose of this study is to determine if two medicines (allopurinol and losartan) can influence heart and blood vessel health compared to placebo in patients with sleep apnea who are using continuous positive airway pressure (CPAP).

Detailed Description

The specific aims of this research project are: 1) Determine if treatment with losartan, an angiotensin type I receptor (AT1R) antagonist, or allopurinol, a XO inhibitor, normalize chemoreflex control of sympathetic outflow and ventilation and improve local vascular regulation and stiffness; and 2) Determine if these interventions reduce the severity of sleep disordered breathing and lower diurnal blood pressure.

Conditions

Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour); Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Losartan

Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.

Allopurinol

Allopurinol 300 mg daily for 6 weeks

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

Allopurinol 300 mg daily for 6 weeks

Placebo

Placebo capsule daily for 6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule daily for 6 weeks

Interventions

Losartan

Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic. Remain at 50 mg daily for 4 more weeks or removed from study if symptomatic.

Intervention Type: DRUG

Allopurinol

Allopurinol 300 mg daily for 6 weeks

Intervention Type: DRUG

Placebo

Placebo capsule daily for 6 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males and females between ages of 21 and 65 years
• Apnea hypopnea index or respiratory disturbance index greater than or equal to 25 events per hour
• Subjects eligible for CPAP or BiPAP therapy
• Hypertension by clinical history/diagnosis (may be controlled with non- exclusionary medications) or average blood pressure > 140/90 mm Hg (using last two measurements in prior 12 months - or 1 prior blood pressure and 1 blood pressure at screening)

Exclusion Criteria

• If subject not using CPAP, having AHI > 60 events/hour or oxygen saturation ≤ 65% during sleep
• Presence of clinical CV disease (coronary artery disease, angina, arrhythmias (subjects with sinus arrhythmias will be reviewed by PI for enrollment), stroke, TIA, cor pulmonale, etc.), heart failure, bruits, or diabetes mellitus by clinical diagnosis/history
• Presence of pulmonary disease that results in significant hypoxemia (resting SaO2 < 88%)
• Hypertriglyceridemia (triglycerides >300 mg/dL), diabetes or impaired glucose tolerance (fasting plasma glucose > 125 mg/dL)
• Patients taking angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, potassium-sparing diuretics (without accompanying loop/thiazide diuretic), allopurinol, oxypurinol, febuxostat, amoxicillin, ampicillin, azathioprine or mercaptopurine.
• Patients with chronic kidney disease (Serum creatinine >1.5 mg/dL) or history of significant hyperkalemia (Serum potassium > 5.2 mEq/L) with ARB therapy
• Patients with history of angioedema
• Patients with bilateral,modified radical or radical mastectomies
• Patients who have a Serum potassium > 5.0 mEq/L at the screening visit
• Female patients who are pregnant (determined by urine pregnancy test) or breastfeeding
• Patients with active MRSA or VRE (vancomycin resistant enterococcus) infection
• History of adverse reaction to allopurinol,losartan, or zolpidem**
• Patients who cannot swallow oral capsules
• Patients who are hospitalized or who have been recently hospitalized (last 2 weeks)
• Inability to comply with or complete the protocol or other reasons at the discretion of the investigators

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Dopp, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

UW Madison School of Pharmacy

Barbara J Morgan, PhD, PT

Role: PRINCIPAL_INVESTIGATOR

UW Madison School of Medicine

Locations

Aurora Bay Care

Green Bay, Wisconsin, United States

Gundersen Lutheran

La Crosse, Wisconsin, United States

University of Wisconsin Madison

Madison, Wisconsin, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Countries

United States

References

Morgan BJ, Teodorescu M, Pegelow DF, Jackson ER, Schneider DL, Plante DT, Gapinski JP, Hetzel SJ, Dopp JM. Effects of losartan and allopurinol on cardiorespiratory regulation in obstructive sleep apnoea. Exp Physiol. 2018 Jul;103(7):941-955. doi: 10.1113/EP087006. Epub 2018 Jun 8.

Reference Type: RESULT

PMID: 29750475 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01HL105365

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A561000

Identifier Type: OTHER

Identifier Source: secondary_id

PHARM/PHARMACY/PHARMACY

Identifier Type: OTHER

Identifier Source: secondary_id

2012-0026

Identifier Type: -

Identifier Source: org_study_id