Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)Phase 2CVD/OSANCT01637623

Study of Cardiovascular Disease and Obstructive Sleep Apnea

A Phase 2 study testing Losartan and Allopurinol in people with Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour) and Hypertension, run by University of Wisconsin, Madison at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 21 to 65 years
Conditions the study is for: Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour), Hypertension
What is being tested?: Losartan and Allopurinol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 87 participants
Where: 4 sitesUnited States
Study dates: Jun 2012to Jun 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Show all 15Show fewer

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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Aurora Bay Care
Green Bay, Wisconsin, 54308
Gundersen Lutheran
La Crosse, Wisconsin, 54601
University of Wisconsin Madison
Madison, Wisconsin, 53705
Marshfield Clinic
Marshfield, Wisconsin, 54449

Other trials in United States

About this study

Official title: Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea

Read the 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.

Conditions: Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour), Hypertension
Being tested: Losartan, Allopurinol, Placebo
Keywords: Hypertension, High Blood Pressure, Sleep Apnea, Obstructive Sleep Apnea, OSA
Medical subject headings: Sleep Apnea, Obstructive, Hypertension, Sleep Apnea Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LosartanDrug
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.
AllopurinolDrug
Allopurinol 300 mg daily for 6 weeks
PlaceboDrug
Placebo capsule daily for 6 weeks

Study groups in NCT01637623
Study group	Role	What they receive
Losartan	Active comparator	Losartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range. Receives: Drug: Losartan
Allopurinol	Active comparator	Allopurinol 300 mg daily for 6 weeks Receives: Drug: Allopurinol
Placebo	Placebo comparator	Placebo capsule daily for 6 weeks Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: baseline and 6 weeks

Secondary outcomes (10)

Change in Aortic Pulse Wave Velocity
measurement of vascular stiffness assessed before and after study drug treatment
Measured: baseline and 6 weeks
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.
Measured: baseline and 6 weeks
Forearm Vascular Conductance
Assessment measurements of forearm vascular conductance during basal conditions and during graded hypoxia before and after study drug treatment.
Measured: baseline and 6 weeks
Change in Minute Ventilation at Normoxia
assessed before and after study drug treatment
Measured: baseline and 6 weeks
Change in Minute Ventilation During Hypoxia
assessed before and after study drug treatment
Measured: baseline and 6 weeks
Aortic Augmentation Index
assessed before and after study drug treatment
Measured: baseline and 6 weeks
Mean Change in PERCENT Vasodilation
Flow-mediated vasodilation (FMD) (measurement of vascular endothelial function) assessed before and after study drug treatment
Measured: baseline and 6 weeks
Apnea-Hypopnea Index
Severity of sleep apnea assessed before and after study drug treatment
Measured: baseline and 6 weeks
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
assessed before and after study drug treatment
Measured: baseline and 6 weeks
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Change in mean 24 hour blood pressure (mean arterial pressure)
Measured: baseline and 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Jun 2015

First posted11 Jul 2012 (estimated)
Study startJun 2012
Primary completionJun 2015
Study completionJun 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)Studies of the same condition, open and under way.
More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 87 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01637623
Sponsor's protocol ID: 2012-0026
Other IDs: U01HL105365, A561000, PHARM/PHARMACY/PHARMACY
Acronym: CVD/OSA
Status last verified: Aug 2020
First submitted: 29 Jun 2012
Last updated: 14 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 29750475

Study at a glance

From the registry record, last updated by the sponsor on 14 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacologic Interventions for Cardiovascular Disease in Obstructive Sleep Apnea
ClinicalTrials.gov ID: NCT01637623
Acronym / sponsor ID: CVD/OSA / 2012-0026
Conditions: Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour), Hypertension
Keywords: Hypertension, High Blood Pressure, Sleep Apnea, Obstructive Sleep Apnea, OSA
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 87 participants (actual)
Lead sponsor: University of Wisconsin, MadisonUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Jun 2012
Primary completion: Jun 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 11 Jul 2012 (estimated)
Results: Posted 14 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Losartan	Active comparator	Drug: LosartanLosartan 50 mg daily for two weeks, then increased to 100mg daily for 4 weeks if asymptomatic and blood pressure within range.
Allopurinol	Active comparator	Drug: AllopurinolAllopurinol 300 mg daily for 6 weeks
Placebo	Placebo comparator	Drug: PlaceboPlacebo capsule daily for 6 weeks

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (15 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LosartanLosartan 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	Losartan
AllopurinolAllopurinol 300 mg daily for 6 weeks	Drug	Allopurinol
PlaceboPlacebo capsule daily for 6 weeks	Drug	Placebo

Primary outcome

Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia
Time frame: baseline and 6 weeks
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.

10 secondary outcomes

Change in Aortic Pulse Wave Velocity
Time frame: baseline and 6 weeks
Cerebrovascular Conductance
Time frame: baseline and 6 weeks
Forearm Vascular Conductance
Time frame: baseline and 6 weeks
Change in Minute Ventilation at Normoxia
Time frame: baseline and 6 weeks
Change in Minute Ventilation During Hypoxia
Time frame: baseline and 6 weeks
Aortic Augmentation Index
Time frame: baseline and 6 weeks
Mean Change in PERCENT Vasodilation
Time frame: baseline and 6 weeks
Apnea-Hypopnea Index
Time frame: baseline and 6 weeks
PERCENT Time Spent Below 88 PERCENT Oxygen Saturation
Time frame: baseline and 6 weeks
Change in Mean 24-Hour Blood Pressure (Mean Arterial Pressure)
Time frame: baseline and 6 weeks

Results and safety

Results posted to the registry on 14 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Losartan	29	28
Allopurinol	30	30
Placebo	28	25

Primary outcome: Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia

Time frame: baseline and 6 weeks. Mean (Standard Deviation). Unit: bursts/minute*%SaO2

Measure	Losartan n = 18	Allopurinol n = 23	Placebo n = 25
Baseline	-0.54 (0.29)	-0.84 (0.47)	-0.71 (0.43)
Following 6 weeks of therapy	-0.69 (.50)	-0.66 (0.38)	-0.61 (0.40)

Population analysed: Data is for fewer subjects than were randomized to treatment because a useable nerve signal was not obtained on all participants.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 6 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Losartan	0 of 29 (0%)	0 of 29 (0%)	0 of 29
Allopurinol	0 of 30 (0%)	0 of 30 (0%)	0 of 30
Placebo	0 of 28 (0%)	0 of 28 (0%)	0 of 28

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 29750475Morgan 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John Dopp, Pharm.D. principal investigator

UW Madison School of Pharmacy

Barbara J Morgan, PhD, PT principal investigator

UW Madison School of Medicine

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Muscle Sympathetic Nerve Activity Responses During Hypoxia (time frame: baseline and 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01637623, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2020.