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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
87
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 300 mg daily for 6 weeks
Placebo capsule daily for 6 weeks
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
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.
Time frame: baseline and 6 weeks
Change in Aortic Pulse Wave Velocity
measurement of vascular stiffness assessed before and after study drug treatment
Time frame: baseline and 6 weeks
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.
Time frame: baseline and 6 weeks
Forearm Vascular Conductance
Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.
Time frame: baseline and 6 weeks
Change in Minute Ventilation at Normoxia
assessed before and after study drug treatment
Time frame: baseline and 6 weeks
Change in Minute Ventilation During Hypoxia
assessed before and after study drug treatment
Time frame: baseline and 6 weeks
Aortic Augmentation Index
assessed before and after study drug treatment
Time frame: baseline and 6 weeks
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Mean Change in PERCENT Vasodilation
Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Time frame: baseline and 6 weeks
Apnea-Hypopnea Index
Severity of sleep apnea assessed before and after study drug treatment
Time frame: baseline and 6 weeks
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
assessed before and after study drug treatment
Time frame: baseline and 6 weeks
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Change in mean 24 hour blood pressure (mean arterial pressure)
Time frame: baseline and 6 weeks