Study of Cardiovascular Disease and Obstructive Sleep Apnea (CVD/OSA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Wisconsin, Madison
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01637623
First received: June 29, 2012
Last updated: June 26, 2014
Last verified: June 2014

June 29, 2012
June 26, 2014
June 2012
June 2015   (final data collection date for primary outcome measure)
Muscle sympathetic nerve activity responses during hypoxia [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
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.
MSNA responses during hypoxia [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
The primary outcome variable is the difference in the individual slope of the MSNA - SaO2 response curve at 6 weeks and baseline between treatment groups.
Complete list of historical versions of study NCT01637623 on ClinicalTrials.gov Archive Site
  • Aortic Pulse Wave Velocity [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    measurement of vascular stiffness assessed before and after study drug treatment
  • Cerebral Blood Flow [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessment measures of cerebral and forearm blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Plasma catecholamine concentrations before and after study drug and change in plasma catecholamines during hypoxia will be assessed as a secondary indicator of sympathetic activation.
  • Forearm Blood Flow [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessment measurements of forearm blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Plasma catecholamines during hypoxia will be assessed as a secondary indicator of sympathetic activation.
  • Minute ventilation at rest and during hypoxia [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Aortic Augmentation Index [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • % Vasodilation [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    Flow-mediated vasodilation (measurement of vascular endothelial function) assessed before and after study drug treatment
  • Apnea Threshold [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Apnea-Hypopnea Index [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • % Time Spent Below 90% Oxygen Saturation [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Mean Blood Pressure [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    Mean 24 hour blood pressure, mean nighttime blood pressure, mean daytime blood pressure, blood pressure load, and night/day pressure ratio assessed before and after study drug treatment
  • Aortic Pulse Wave Velocity [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    measurement of vascular stiffness assessed before and after study drug treatment
  • Cerebral Blood Flow [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessment measures of cerebral and forearm blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Plasma catecholamine concentrations before and after study drug and change in plasma catecholamines during hypoxia will be assessed as a secondary indicator of sympathetic activation.
  • Forearm Blood Flow [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessment measurements of forearm blood flow during basal conditions and during graded hypoxia before and after study drug treatment. Plasma catecholamines during hypoxia will be assessed as a secondary indicator of sympathetic activation.
  • Ventilation Outcome Variable [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Aortic Augmentation Index [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • % Vasodilation [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    Flow-mediated vasodilation (measurement of vascular endothelilal function) assessed before and after study drug treatment
  • Apnea Threshold [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Apnea-Hypopnea Index [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • % Time Spent Below 90% Oxygen Saturation [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    assessed before and after study drug treatment
  • Mean Blood Pressure [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    Mean 24 hour blood pressure, mean nighttime blood pressure, mean daytime blood pressure, blood pressure load, and night/day pressure ratio assessed before and after study drug treatment
Not Provided
Not Provided
 
Study of Cardiovascular Disease and Obstructive Sleep Apnea
Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)
  • Hypertension
  • 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.
  • Drug: Allopurinol
    Allopurinol 300 mg daily for 6 weeks
  • Drug: Placebo
    Placebo capsule daily for 6 weeks
  • Active Comparator: Losartan
    Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
    Intervention: Drug: Losartan
  • Active Comparator: Allopurinol
    Allopurinol 300 mg daily for 6 weeks
    Intervention: Drug: Allopurinol
  • Placebo Comparator: Placebo
    Placebo capsule daily for 6 weeks
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Both
21 Years to 65 Years
No
Contact: John Dopp, Pharm.D. 608-265-9352 jmdopp@pharmacy.wisc.edu
Contact: Meghan Hackbarth, BS 608-265-8765 mmhack@clinicaltrials.wisc.edu
United States
 
NCT01637623
NIHU0120120026, U01HL105365
Yes
University of Wisconsin, Madison
University of Wisconsin, Madison
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: John Dopp, Pharm.D. UW Madison School of Pharmacy
Principal Investigator: Barbara J Morgan, PhD, PT UW Madison School of Medicine
University of Wisconsin, Madison
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP