Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea

NCT05804084 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 802041K23HL161336
• Study Type: interventional
• Target: 60
• 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, memory problems and can severely affect quality of life. 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. 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. Further, its low cost (66¢/day) and once-daily dosing may be attractive for OSA patients unable or unwilling to wear a mask each night. But previous studies had many limitations such as studying acetazolamide for only a few days and not capturing important outcomes. The goal of this study is to test if acetazolamide can improve sleep apnea, neurocognitive function and quality of life in adults with OSA, and to assess how it does that. Thus, the investigators will treat 60 OSA patients with acetazolamide or placebo for 4 weeks each. The order in which participants receive the drug or placebo will be randomized. At the end of each 4 week period the investigators will assess OSA severity, neurocognitive function and quality of life. 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. 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; Acetazolamide; Precision medicine

Outcome Measures

Primary Outcomes (1)

• Apnea Hypopnea Index (AHI)

  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. Alternative definitions of the AHI will be explored as well (e.g. hypopneas based on 4% desaturations, or position/sleep-stage specific AHIs).

  4 weeks

Secondary Outcomes (11)

• Hypoxic Burden (percent*minute/hour)

  4 weeks

• Overnight Memory Improvement (change in percentage points)

  4 weeks

• Cognitive function composite score

  4 weeks

• Response Speed

  4 weeks

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

  4 weeks

Other Outcomes (1)

• Sleep Apnea Traits with special focus on loop gain

  4 weeks

Study Arms (2)

Acetazolamide, then Placebo

EXPERIMENTAL

Subjects will start with a 4-week ACETAZOLAMIDE regimen Day 1-27: Acetazolamide 500mg at bedtime at home Day 28: Acetazolamide 500mg at bedtime in the sleep laboratory After a wash-out period, subjects will then cross-over to a 4-week PLACEBO regimen: Day 1-27: Placebo (matching Acetazolamide 500mg) at bedtime at home Day 28: Placebo (matching Acetazolamide 500mg) at bedtime in the sleep laboratory

Drug: Acetazolamide; Drug: Placebo

Placebo, then Acetazolamide

EXPERIMENTAL

Subjects will start with a 4-week PLACEBO regimen Day 1-27: Placebo (matching Acetazolamide 500mg) at bedtime at home Day 28: Placebo (matching Acetazolamide 500mg) at bedtime in the sleep laboratory After a wash-out period, subjects will then cross-over to a 4-week ACETAZOLAMIDE regimen: Day 1-27: Acetazolamide 500mg at bedtime at home Day 28: Acetazolamide 500mg at bedtime in the sleep laboratory

Drug: Acetazolamide; Drug: Placebo

Interventions

Acetazolamide DRUG

Acetazolamide tablet (encapsulated)

Also known as: Diamox

Acetazolamide, then Placebo; Placebo, then Acetazolamide

Placebo DRUG

Sugar capsule manufactured to match encapsulated Acetazolamide

Acetazolamide, then Placebo; Placebo, then Acetazolamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Body mass index ≤ 35 kg/m2
• Untreated moderate/severe OSA (AHI ≥15/h)

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)
• Abnormally low blood counts/electrolytes or renal function at baseline
• Use of OSA therapy during the past 1 month, or plans to urgently resume/(re)start clinical OSA therapy within 3 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)
• 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
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UC San Diego; Altman Clinical and Translational Research Institute Building

La Jolla, California, 92121, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Acetazolamide

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

Study Officials

• Christopher N Schmickl, MD, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pamela DeYoung, RPSGT

CONTACT

858 246 2183; sleepresearch@health.ucsd.edu

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: March 27, 2023
• First Posted: April 7, 2023
• Study Start: May 16, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)