Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Diego

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

Body mass index ≤ 35 kg/m2

Untreated moderate/severe OSA (AHI ≥15/h)

Disqualifiers

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

Trial design

Design model

Crossover

Treatments tested in this trial

  • Acetazolamide

    Drug

    Acetazolamide tablet (encapsulated)

  • Placebo

    Drug

    Sugar capsule manufactured to match encapsulated Acetazolamide

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Acetazolamide, then PlaceboExperimental treatment 2 interventions
Group B: Placebo, then AcetazolamideExperimental treatment 2 interventions

Trial outcomes

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).

Time frame
4 weeks

Secondary outcomes

1

Hypoxic Burden (percent*minute/hour)

Respiratory event-associated area under the desaturation curve from pre-event baseline (continuous outcome with units being "percent\*minutes/hour")

Time frame
4 weeks
2

Overnight Memory Improvement (change in percentage points)

Based on Verbal Paired-Associates task

Time frame
4 weeks
3

Cognitive function composite score

Total composite score from the National Institutes of Health (NIH) Toolbox based on 7 cognitive domains which will also be explored separately and via subscales (i.e., (Fluid and Crystaliized Cognition Composite Scores). These scores are based on a T-Score metric, with a normative mean of 50 and an SD of 10. Higher scores indicate better cognitive function.

Time frame
4 weeks
4

Response Speed

10-minute Psychomotor vigilance task (PVT)

Time frame
4 weeks

Other outcomes

1

Sleep Apnea Traits with special focus on loop gain

Quantified from routine polysomnography data.

Time frame
4 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, San Diego

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator