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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Spironolactone; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Spironolactone; 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; 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.
PLACEBO_COMPARATOR: Placebo; Placebo and will receive treatment as usual for obstructive sleep apnea.	Drug: Placebo; Subjects assigned to the placebo group will take one pill for the first 4 weeks and a second pill for the remaining 8 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Louise O'Brien, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2022
• Primary Completion (ANTICIPATED): April 1, 2023
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: December 11, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (ACTUAL): December 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Spironolactone; Positive Airway Pressure
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: HUM00147375

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study team does not have plans to actively share data, however, they are open to collaboration following contact with the investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No