Spironolactone to Improve Apnea and Cardiovascular Markers in Obstructive Sleep Apnea Patients

Study Overview
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Brief Summary
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The purpose of this study is to test whether Spironolactone can improve the severity of obstructive sleep apnea and improve cardiovascular biomarkers in people who are not regularly using their Positive Airway Pressure (PAP) therapy.

Official Title
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Spironolactone to Improve Apnea and Cardiovascular Markers in Obstructive Sleep Apnea Patients With Cardiovascular Disease Who Are Non-Adherent With Positive Airway Pressure: A Randomized Placebo-Controlled Pilot Trial

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) greater than or equal to 30 Diagnosis of moderate to severe OSA via diagnostic polysomnography (AHI≥15) or home sleep apnea test (respiratory event index (REI)≥15). Diagnosis of cardiovascular disease Meet criteria for hypertension (minimum systolic blood pressure ≥ 140 but <180) Prescribed PAP therapy but non-adherent (failure to use PAP for at least 4 hours per night on minimum 5/7 nights per week on average over a one-month period) Exclusion Criteria: Diagnosis of congestive heart failure; resistant hypertension; hepatic disease; Addison's disease; cancer; or recent (past 3 months) myocardial infarction, or stroke Diagnosis of central sleep apnea Patients who are not using PAP at all (untreated) or using another form of treatment for OSA Currently taking, recent trial (past month), or allergy for spironolactone Severe respiratory disease (e.g., diagnosis of chronic obstructive pulmonary disease, uncontrolled asthma) History of leukopenia and/or thrombocytopenia Current use of another potassium sparing diuretic (e.g., amiloride or eplerenone) Current use of lithium, barbiturates, narcotics, muscle relaxants, pressor amines, or cholestyramine Patients who plan to have surgery during the time period of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The researchers will do a trial of spironolactone in 30 obstructive sleep apnea (OSA) patients with cardiovascular disease who are non-adherent with Positive Airway Pressure (PAP) therapy.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spironolactone<br>Dose of 25 mg daily that may be titrated up to 50 mg daily, if tolerated and will receive treatment as usual for obstructive sleep apnea. | Drug: Spironolactone<br>* If tolerated and serum potassium <5.0 meq/L, the dose will be increased to 50 mg (2 pills) after 4 weeks. If serum potassium is >5.0 but less than 5.5 or creatinine >4.0 mg/dL, the dose will be adjusted to 25 mg every other day; if potassium levels ≥5.5 in a non-hemolyzed blood sample, the medication will be discontinued.<br>|
| Placebo Comparator: Placebo<br>Placebo and will receive treatment as usual for obstructive sleep apnea. | Drug: Placebo<br>* Subjects assigned to the placebo group will take one pill for the first 4 weeks and a second pill for the remaining 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in apnea-hypopnea index (AHI) | AHI is obtained from polysomnography studies | Day 0, Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in minimum oxygen saturation (SaO2) | Oxygen saturation is obtained from polysomnography studies | Day 0, Day 84 | 
| Change in Inflammatory biomarker | Biomarkers of interest will be obtained via blood draws. Markers of interest: Interleukin 6 protein (IL-6), Tumor necrosis factor alpha (TNF α), High Sensitivity C-Reactive Protein, Brain Natriuretic Peptide (BNP), and procollagen 1 and 3. | Day 0, Day 84 | 
| Change in Diurnal blood pressure | Measured using SPRINT methods; Seated blood pressure is measured after a rest period using an automated device or manual devices if necessary. The preferred method is the automated device. Both systolic and diastolic blood pressure will be measured. | Day 0, Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spironolactone, Positive Airway Pressure