Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

— PANACEA  

Official title:

Patient-centered and Neurocognitive Outcomes With Acetazolamide for Sleep Apnea

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05804084
• Other study ID #: 802041
• Secondary ID: K23HL161336
• Status: Recruiting
• Phase: Phase 2
• Start date: May 16, 2023
• Est. completion date: October 31, 2026

Study information

• Verified date: August 2023
• Source: University of California, San Diego
• Contact: Pamela DeYoung, RPSGT
• Phone: 858 246 2183
• Email: sleepresearch[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

The goal of this randomized, controlled, double-blind clinical trial is to compare the medication acetazolamide 500mg/day against placebo in adults who have at least moderate severe obstructive sleep apnea. The main questions this trial aims to answer are:

Is acetazolamide for 4 weeks more effective than placebo for treating obstructive sleep apnea? Is acetazolamide for 4 weeks more effective than placebo for improving neurocognitive function and quality of life? What are potential predictors and mechanisms of improvements with acetazolamide in sleep apnea, neurocognitive function and quality of life?

Participants will undergo the following activities:

• Eligibility screening (online or via phone; ~10min)

• Subjects who screen positive: in-person eligibility assessment (~1h) including a history, exam, blood testing, plus an overnight home sleep test

• Participants who are eligible: will come to the research lab (~15min) and be provided with a 4-week supply of the first study drug (i.e. acetazolamide or placebo) to be taken each night at home. Neither the researchers, nor the participants will know whether participants received acetazolamide or placebo. During this 4-week period, participants will wear a watch-sized activity tracker to measure their sleep amount and researchers will check in on participants weekly; at the end of the 4-week period participants are asked to come in for an overnight visit (~12h) which includes the following activities: general exam, questionnaires (e.g. quality of life), blood test, neurocognitive function tests, and an overnight sleep study to assess the severity of sleep apnea

Researchers will compare the effects of acetazolamide on sleep apnea severity, neurocognitive function and quality of life with the effects of placebo to see if acetazolamide may be an effective treatment for select patients with sleep apnea.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years

• Body mass index = 35 kg/m2

• Untreated moderate/severe OSA (AHI =15/h)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Acetazolamide
Acetazolamide tablet (encapsulated)
• Placebo
Sugar capsule manufactured to match encapsulated Acetazolamide

Locations

Country	Name	City	State
United States	UC San Diego; Altman Clinical and Translational Research Institute Building	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sleep Apnea Traits with special focus on loop gain	Quantified from routine polysomnography data.	4 weeks
Primary	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	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")	4 weeks
Secondary	Overnight Memory Improvement (change in percentage points)	Based on Verbal Paired-Associates task	4 weeks
Secondary	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.	4 weeks
Secondary	Response Speed	10-minute Psychomotor vigilance task (PVT)	4 weeks
Secondary	Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SDA) instrument	Based on response pattern scoring, the PROMIS 8-item SDA score will be converted into a T-score with a mean of 50 (reflecting the average for the United States general population) and a standard deviation of 10. Higher t-scores reflect greater sleep disturbance.	4 weeks
Secondary	Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) instrument	Based on response pattern scoring, the PROMIS 8-item SRI score will be converted into a T-score with a mean of 50 (reflecting the average for the United States general population) and a standard deviation of 10. Higher t-scores reflect greater sleep-related impairment.	4 weeks
Secondary	Epworth Sleepiness Scale (ESS) Score	The ESS is an 8-item instrument assessing the likelihood of dozing off in 8 different situations with points for each item ranging from 0 to 3 (0 = would never doze off; 3 = high chance of dozing off). The points for each item are summed up, thus the total score ranges from 0 to 24, with higher ESS scores indicating greater sleepiness.	4 weeks
Secondary	Functional Outcomes of Sleep Questionnaire 10 (FOSQ-10)	The FOSQ-10 is a 10-item instrument assessing sleep-related quality of life across 5 domains (general productivity, activity level, vigilance, social outcomes, intimacy and sexual relationships). Each item is scored on a scale ranging from 1 to 4 (a higher number indicates a better functional status for that item).; The mean scores of the 5 subscales are averaged and then multiplied by 5 to calculate a total summary score ranging from 5-20 (higher scores indicate better functional outcomes). The main focus will be on the total summary score, but scores from subscales will be explored as well.	4 weeks
Secondary	Short Form 36 (SF-36) Health Survey	The SF36 is a widely used questionnaire to measure general health-related quality of life across 8 domains (e.g. physical functioning, Energy/fatigue, Social functioning, etc). The score for each of the 8 domains ranges from 0 to 100, with greater scores indicating better health-related quality fo life in this domain.	4 weeks
Secondary	Mean blood pressure	Average mean blood pressure based on two resting blood pressure measurements. Systolic/diastolic blood pressures will be explored as well.	4 weeks
Secondary	Reactive hyperemia index	Based on a device called EndoPAT, which measures non-invasively bloodflow before, during, and after 5-minutes of occlusion to one arm.	4 weeks