Back to resultsStudy of Cardiovascular Disease and Obstructive Sleep Apnea (CVD/OSA)
Primary Purpose
Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour), Hypertension
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Losartan
Allopurinol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour) focused on measuring Hypertension, High Blood Pressure, Sleep Apnea, Obstructive Sleep Apnea, OSA
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
Sites / Locations
- Aurora Bay Care
- Gundersen Lutheran
- University of Wisconsin Madison
- Marshfield Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Losartan
Allopurinol
Placebo
Arm Description
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Allopurinol 300 mg daily for 6 weeks
Placebo capsule daily for 6 weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change in Aortic Pulse Wave Velocity
measurement of vascular stiffness assessed before and after study drug treatment
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.
Forearm Vascular Conductance
Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.
Change in Minute Ventilation at Normoxia
assessed before and after study drug treatment
Change in Minute Ventilation During Hypoxia
assessed before and after study drug treatment
Aortic Augmentation Index
assessed before and after study drug treatment
Mean Change in PERCENT Vasodilation
Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Apnea-Hypopnea Index
Severity of sleep apnea assessed before and after study drug treatment
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
assessed before and after study drug treatment
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Change in mean 24 hour blood pressure (mean arterial pressure)
Full Information
NCT ID
NCT01637623
First Posted
June 29, 2012
Last Updated
August 13, 2020
Sponsor
University of Wisconsin, Madison
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT01637623
Brief Title
Study of Cardiovascular Disease and Obstructive Sleep Apnea
Acronym
CVD/OSA
Official Title
Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour), Hypertension
Keywords
Hypertension, High Blood Pressure, Sleep Apnea, Obstructive Sleep Apnea, OSA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Losartan
Arm Type
Active Comparator
Arm Description
Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Arm Title
Allopurinol
Arm Type
Active Comparator
Arm Description
Allopurinol 300 mg daily for 6 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsule daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Losartan
Intervention Description
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
Intervention Name(s)
Allopurinol
Intervention Description
Allopurinol 300 mg daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsule daily for 6 weeks
Primary Outcome Measure Information:
Title
Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
Description
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
Secondary Outcome Measure Information:
Title
Change in Aortic Pulse Wave Velocity
Description
measurement of vascular stiffness assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Cerebrovascular Conductance
Description
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
Title
Forearm Vascular Conductance
Description
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
Title
Change in Minute Ventilation at Normoxia
Description
assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Change in Minute Ventilation During Hypoxia
Description
assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Aortic Augmentation Index
Description
assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Mean Change in PERCENT Vasodilation
Description
Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Apnea-Hypopnea Index
Description
Severity of sleep apnea assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
Description
assessed before and after study drug treatment
Time Frame
baseline and 6 weeks
Title
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Description
Change in mean 24 hour blood pressure (mean arterial pressure)
Time Frame
baseline and 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Dopp, Pharm.D.
Organizational Affiliation
UW Madison School of Pharmacy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara J Morgan, PhD, PT
Organizational Affiliation
UW Madison School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aurora Bay Care
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54308
Country
United States
Facility Name
Gundersen Lutheran
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
University of Wisconsin Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Marshfield Clinic
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29750475
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.
Results Reference
result
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Study of Cardiovascular Disease and Obstructive Sleep Apnea
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