Study of Cardiovascular Disease and Obstructive Sleep Apnea

Hypertension Clinical Trial

— CVD/OSA  

Official title:

Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01637623
• Other study ID #: 2012-0026
• Secondary ID: U01HL105365A5610
• Status: Completed
• Phase: Phase 2
• Start date: June 2012
• Est. completion date: June 2015

Study information

• Verified date: August 2020
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Cardiovascular Diseases
• Hypertension
• Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• 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.
• Allopurinol
Allopurinol 300 mg daily for 6 weeks
• Placebo
Placebo capsule daily for 6 weeks

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia	The primary outcome variable is the change in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.	baseline and 6 weeks
Secondary	Change in Aortic Pulse Wave Velocity	measurement of vascular stiffness assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Cerebrovascular Conductance	Assessment measures of cerebral blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Cerebrovascular conductance (CVC) was calculated as velocity-time integral/mean arterial pressure.	baseline and 6 weeks
Secondary	Forearm Vascular Conductance	Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.	baseline and 6 weeks
Secondary	Change in Minute Ventilation at Normoxia	assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Change in Minute Ventilation During Hypoxia	assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Aortic Augmentation Index	assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Mean Change in PERCENT Vasodilation	Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Apnea-Hypopnea Index	Severity of sleep apnea assessed before and after study drug treatment	baseline and 6 weeks
Secondary	PERCENT Time Spent Below 88 PERCENT Oxygen Saturation	assessed before and after study drug treatment	baseline and 6 weeks
Secondary	Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)	Change in mean 24 hour blood pressure (mean arterial pressure)	baseline and 6 weeks