Acetazolamide for Obstructive Sleep Apnea to Improve Heart Health

NCT05616260 | Completed Phase 2 FDA Drug

• 1 other identifier: 804081
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea (OSA) is a severe type of snoring causing people to choke in their sleep. It affects millions of Americans, causing many health problems. For example, patients with OSA often feel very sleepy and are at risk of falling asleep while driving. OSA also causes elevated blood pressure increasing the risk for heart attacks and strokes. Patients with OSA are often treated with a face-mask that helps them breath at night but can be difficult to tolerate. In fact, about half the patients eventually stop using this mask. Because there are few other treatments (and no drug therapy), many OSA patients are still untreated. Of note, especially young adults (i.e. 18 to 50 years old) benefit from treating their OSA, but they are also less likely to use the mask. Acetazolamide (a mild diuretic drug) has been used for over 50 years to treat many different conditions and is well tolerated. Recent data suggest, that acetazolamide may help OSA patients to not choke in their sleep and lower their blood pressure. Especially young adults with OSA are likely to respond well to this drug. Further, its low cost (66¢/day) and once- daily dosing may be particularly attractive for young OSA patients unable or unwilling to wear a mask each night. But previous studies had many limitations and did not focus on young adults. The goal of this study is to test if acetazolamide can improve sleep apnea and cardiovascular health in young adults with OSA (18-50 years old), and how it does that. Thus, we will treat 46 young OSA patients with acetazolamide or placebo for 2 weeks each. The order in which participants receive the drug or placebo will be randomized. At the end of each 2 week period we will assess OSA severity and cardiovascular health. Thus, this study will help assess acetazolamide's potential value for OSA treatment, and may also help to identify patients who are most likely to respond to acetazolamide (including select individuals \>50 years of age). Ultimately, this work promises a drug therapy option for millions of OSA patients who are unable to tolerate current treatments.

Conditions

Obstructive Sleep Apnea

Keywords

obstructive sleep apnea; OSA; CPAP; Acetazolamide

Outcome Measures

Primary Outcomes (2)

• Apnea Hypopnea Index

  The AHI is a measure of sleep apnea severity and is defined as the number of apneas (no breathing for 10+ seconds) and hypopneas (reduced breathing for 10+ seconds associated with a \>=3% desaturation or cortical arousal) per hour of sleep.

  14 days

• 24-hour Mean Blood Pressure

  Based on 24h blood pressure measurements

  14 days

Secondary Outcomes (8)

• Hypoxic Burden

  14 days

• Reactive Hyperemia Index

  14 days

• Response Speed

  14 days

• Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SDA) instrument

  14 days

• Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) instrument

  14 days

Other Outcomes (4)

• Measures of Heart-rate Variability

  14 days

• Overnight Memory Improvement (%)

  14 days

• Short Form 36 (SF-36) Health Survey

  14 days

Study Arms (2)

Acetazolamide, then Placebo, then optional open-label CPAP-therapy

EXPERIMENTAL

Subjects will start with a 2-week ACETAZOLAMIDE regimen * Day 1-13: Acetazolamide 500mg at bedtime at home * Day 14: Acetazolamide 500mg at bedtime in the sleep laboratory After a wash-out period, subjects will then cross-over to a 2-week PLACEBO regimen: * Day 1-13: Placebo (matching Acetazolamide 500mg) at bedtime at home * Day 14: Placebo (matching Acetazolamide 500mg) at bedtime in the sleep laboratory After a wash-out period, subjects may then undergo an OPTIONAL, OPEN-LABEL 2-week CPAP regimen: \- Day 1-14: CPAP will be used at home during sleep

Drug: Acetazolamide; Drug: Placebo; Device: Continuous Positive Airway Pressure

Placebo, then Acetazolamide, then optional open-label CPAP-therapy

EXPERIMENTAL

Subjects will start with a 2-week PLACEBO regimen * Day 1-13: Placebo (matching Acetazolamide 500mg) at bedtime at home * Day 14: Placebo (matching Acetazolamide 500mg) at bedtime in the sleep laboratory After a wash-out period, subjects will then cross-over to a 2-week ACETAZOLAMIDE regimen: * Day 1-13: Acetazolamide 500mg at bedtime at home * Day 14: Acetazolamide 500mg at bedtime in the sleep laboratory After a wash-out period, subjects may then undergo an OPTIONAL, OPEN-LABEL 2-week CPAP regimen: \- Day 1-14: CPAP will be used at home during sleep

Drug: Acetazolamide; Drug: Placebo; Device: Continuous Positive Airway Pressure

Interventions

Acetazolamide DRUG

Acetazolamide tablet (encapsulated)

Also known as: Diamox

Acetazolamide, then Placebo, then optional open-label CPAP-therapy; Placebo, then Acetazolamide, then optional open-label CPAP-therapy

Placebo DRUG

Sugar capsule manufactured to match encapsulated Acetazolamide

Acetazolamide, then Placebo, then optional open-label CPAP-therapy; Placebo, then Acetazolamide, then optional open-label CPAP-therapy

Continuous Positive Airway Pressure DEVICE

Standard CPAP device

Also known as: CPAP

Acetazolamide, then Placebo, then optional open-label CPAP-therapy; Placebo, then Acetazolamide, then optional open-label CPAP-therapy

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 50 years
• Body mass index ≤ 35 kg/m2
• Untreated OSA (AHI ≥10/h)
• Abnormal blood pressure (\>120/80mmHg, or on stable anti-hypertensive therapy for \>1month)

You may not qualify if:

• Substantial sleep hypoxemia (SpO2\<80% for \>10% of the monitoring time during the home sleep test, or for \>25% of the total sleep time during any of the in-laboratory studies)
• Severe uncontrolled hypertension (\>160/110mmHg during baseline assessment; \>180/120mmHg during follow up assessments)
• Abnormally low blood counts/electrolytes or renal function at baseline
• Mean use of OSA therapy ≥ 1h/night during past 1 month, or plans to urgently resume/(re)start clinical OSA therapy within 2 months
• Significant, uncontrolled cardiac, pulmonary, endocrine, renal, hepatic, neurocognitive, psychiatric, or urologic (e.g., kidney stones) disorder
• Other major sleep disorder (e.g., narcolepsy)
• Urgent need to initiate effective OSA therapy (i.e., Epworth sleepiness score \>18, commercial driver, prior sleep-related car accident, or based on MD judgment)
• Severe allergy to sulfa-drugs or taking another carbonic-anhydrase inhibitor (e.g., topiramate, zonisamide)
• Pregnancy/breastfeeding (current/planned)
• Prisoners
• Illicit substance abuse or \>2 standard drinks of alcohol/day
• Medications that may affect OSA or ventilatory control (e.g., opiates, sedatives)
• Thiazide/loop diuretic (risk of hypokalemia)
• Inability to give consent or follow procedures
• Safety concern based on MD judgment

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UC San Diego; Altman Clinical and Translational Research Institute Building

La Jolla, California, 92121, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Acetazolamide; Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Christopher Schmickl, MD, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized, double-blind, placebo-controlled, cross-over trial.

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: December 2, 2022
• Primary Completion: May 13, 2025
• Study Completion: May 13, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)