Acetazolamide for Obstructive Sleep Apnea to Improve Heart Health

Obstructive Sleep Apnea Clinical Trial

— ACE-Of-HEARTs  

Official title:

Acetazolamide for Obstructive Sleep Apnea to Improve Heart Health

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05616260
• Other study ID #: 804081
• Status: Recruiting
• Phase: Phase 2
• Start date: December 2, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• 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 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.

Description:

The goal of this randomized, controlled, double-blind clinical trial is to compare the medication acetazolamide 500mg/day against placebo in young adults (i.e. 18 to 50 years old) who have obstructive sleep apnea and a high blood pressure. The main questions this trial aims to answer are:

• Is acetazolamide for 2 weeks more effective than placebo for treating obstructive sleep apnea?

• Is acetazolamide for 2 weeks more effective than placebo for improving cardiovascular health including blood pressure?

• What are potential predictors and mechanisms of improvements with acetazolamide in sleep apnea and cardiovascular health?

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 2-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 2-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 2-week period participants are asked to wear a 24-hour blood pressure monitor and then come in for an overnight visit (~12h) which includes the following activities: general exam, questionnaires, blood test, measures of cardiovascular health (e.g. blood pressure) and neurocognitive function (e.g. a memory test), and an overnight sleep study to assess the severity of sleep apnea

• Participants will then receive a 2-week supply of the other study drug (i.e. acetazolamide or placebo) and repeat all the activities

• Optional: after completing the activities above, participants who are interested in using continuous positive airway pressure (CPAP) and are deemed good candidates for this approach by the investigators, will be offered 2-weeks of CPAP and repeat the same activities as were done when taking the study drugs (except there will be no overnight sleep study).

Researchers will compare the effects of acetazolamide on sleep apnea severity and cardiovascular health with the effects of placebo (and CPAP) to see if acetazolamide may be an effective treatment for select patients with sleep apnea.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 31, 2024
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• 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)

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)

• 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

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

Device:
• Continuous Positive Airway Pressure
Standard CPAP device

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measures of Heart-rate Variability	Based on 5 min awake, supine ECG sampled at >250Hz	14 days
Other	Overnight Memory Improvement (%)	Based on Verbal Paired-Associates task	14 days
Other	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.	14 days
Other	Sleep Apnea Traits with special focus on loop gain	Quantified from routine polysomnography data.	14 days
Primary	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
Primary	24-hour Mean Blood Pressure	Based on 24h blood pressure measurements	14 days
Secondary	Hypoxic Burden	Respiratory event-associated area under the desaturation curve from pre-event baseline	14 days
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.	14 days
Secondary	Response Speed	Based on 10-minute Psychomotor vigilance task (PVT)	14 days
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.	14 days
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.	14 days
Secondary	Epworth Sleepiness Scale (ESS)	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.	14 days
Secondary	24-hour Mean Systolic Blood Pressure	Based on 24h blood pressure measurements	14 days
Secondary	24-hour Mean Diastolic Blood Pressure	Based on 24h blood pressure measurements	14 days