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
  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:


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 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


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 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Meghan Hackbarth, BS 608-265-8765 mmhack@clinicaltrials.wisc.edu

Locations
United States, Wisconsin
Aurora Bay Care Recruiting
Green Bay, Wisconsin, United States, 54308
Contact: Taylor McGinnis, BS    920-288-3127    Taylor.McGinnis@aurorabaycare.com   
Principal Investigator: James P Gapinski, MD         
Gundersen Lutheran 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: Meghan Hackbarth, BS    608-265-8765    mmhack@clinicaltrials.wisc.edu   
Principal Investigator: John M Dopp, Pharm.D.         
Principal Investigator: Barbara J Morgan, PhD, PT         
Marshfield Clinic Recruiting
Marshfield, Wisconsin, United States, 54449
Contact: Kathy Mancl    715-389-3748    mancl.kathleen@mcrf.mfldclin.edu   
Principal Investigator: Jaime Boero, MD, PhD.         
Sponsors and Collaborators
University of Wisconsin, Madison
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: June 26, 2014
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:
Sleep Apnea, Obstructive
Apnea
Sleep Apnea Syndromes
Respiration Disorders
Sleep Disorders, Intrinsic
Sleep Disorders
Cardiovascular Diseases
Hypertension
Respiratory Tract Diseases
Dyssomnias
Nervous System Diseases
Vascular Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Losartan
Allopurinol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on September 16, 2014