Clinical trial NCT01637623: Study of Cardiovascular Disease and Obstructive Sleep Apnea
Official title: Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)
Hypertension
Keywords: Hypertension
High Blood Pressure
Sleep Apnea
Obstructive Sleep Apnea
OSA
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-07-11
Enrollment: 87
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
timeFrame: baseline and 6 weeks
Secondary outcomes:
measure: Change in Aortic Pulse Wave Velocity
timeFrame: baseline and 6 weeks
measure: Cerebrovascular Conductance
timeFrame: baseline and 6 weeks
measure: Forearm Vascular Conductance
timeFrame: baseline and 6 weeks
measure: Change in Minute Ventilation at Normoxia
timeFrame: baseline and 6 weeks
measure: Change in Minute Ventilation During Hypoxia
timeFrame: baseline and 6 weeks
measure: Aortic Augmentation Index
timeFrame: baseline and 6 weeks
measure: Mean Change in PERCENT Vasodilation
timeFrame: baseline and 6 weeks
measure: Apnea-Hypopnea Index
timeFrame: baseline and 6 weeks
measure: PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
timeFrame: baseline and 6 weeks
measure: Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
timeFrame: baseline and 6 weeks
Other outcomes:
Locations:
city: Green Bay
country: United States
facility: Aurora Bay Care
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Madison
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
Study officials:
affiliation: UW Madison School of Pharmacy
name: John Dopp, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UW Madison School of Medicine
name: Barbara J Morgan, PhD, PT
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.