Study of Cardiovascular Disease and Obstructive Sleep Apnea - Full Text View

Purpose

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).

Condition	Intervention	Phase
Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour) Hypertension	Drug: Losartan Drug: Allopurinol Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure Sleep Apnea

Drug Information available for: Allopurinol Allopurinol sodium Losartan Losartan potassium

U.S. FDA Resources

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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 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

Estimated Enrollment:	150
Study Start Date:	June 2012
Estimated Primary Completion Date:	June 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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.
Active Comparator: Allopurinol Allopurinol 300 mg daily for 6 weeks	Drug: Allopurinol Allopurinol 300 mg daily for 6 weeks
Placebo Comparator: Placebo Placebo capsule daily for 6 weeks	Drug: Placebo Placebo capsule daily for 6 weeks

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

Ages Eligible for Study:	21 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females between ages of 21 and 55 years
Apnea hypopnea index greater than 30 events per hour
Subjects eligible for CPAP therapy
Subjects on CPAP required to have 3 months or more of treatment
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 3 months - 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 >150 mg/dL), diabetes or impaired glucose tolerance (fasting plasma glucose > 100 mg/dL)
Patients taking angiotensin converting enzyme inhibitors, beta blockers, phosphodiesterase type 5 inhibitors, alpha blockers, 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01637623

Contacts

Contact: John Dopp, Pharm.D.	608-265-9352	jmdopp@pharmacy.wisc.edu
Contact: Darcy Bartlett, BSN, MS	608-263-5536	dbartlett@wisc.edu

Locations

United States, Wisconsin
Aurora Bay Care	Not yet recruiting
Green Bay, Wisconsin, United States, 54308
Contact: Sarah Jadin, MS, RD 920-288-3129 sarah.jadin@aurorabaycare.com
Principal Investigator: James P Gapinski, MD
Gundersen Lutheran	Not yet recruiting
LaCrosse, Wisconsin, United States, 54601
Contact: Shelly Clements 608-775-6781 rmclemen@gundluth.org
Principal Investigator: Daren Tobert, MD
University of Wisconsin Madison	Recruiting
Madison, Wisconsin, United States, 53705
Contact: John M Dopp, Pharm.D, 608-265-9352 jmdopp@pharmacy.wisc.edu
Contact: Darcy Bartlett, BSN, MS 608-263-5536 dbartlett@wisc.edu
Principal Investigator: John M Dopp, Pharm.D.
Principal Investigator: Barbara J Morgan, PhD, PT
Marshfield Clinic	Not yet recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Kathy Mancl 715-389-3748 mancl.kathleen@mcrf.mfldclin.edu
Contact: Vanessa Grams 715-221-6069 grams.vanessa@mcrf.mfldclin.edu
Principal Investigator: Jaime Boero, MD, PhD.

Sponsors and Collaborators

University of Wisconsin, Madison

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	John Dopp, Pharm.D.	UW Madison School of Pharmacy
Principal Investigator:	Barbara J Morgan, PhD, PT	UW Madison School of Medicine

More Information

No publications provided

Responsible Party:	University of Wisconsin, Madison
ClinicalTrials.gov Identifier:	NCT01637623 History of Changes
Other Study ID Numbers:	NIHU0120120026, U01HL105365
Study First Received:	June 29, 2012
Last Updated:	July 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Wisconsin, Madison:

Hypertension
High Blood Pressure
Sleep Apnea
Obstructive Sleep Apnea
OSA

Additional relevant MeSH terms:

Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Sleep Disorders, Intrinsic
Sleep Disorders
Cardiovascular Diseases
Hypertension
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Vascular Diseases
Dyssomnias
Nervous System Diseases
Allopurinol

Losartan
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents

ClinicalTrials.gov processed this record on June 17, 2013

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