Acetazolamide for Obstructive Sleep Apnea

(ACE-Of-HEARTs Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Christopher Schmickl, MD, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of California, San Diego

Must not be taking: Opiates, Sedatives, Thiazide/loop diuretics

Disqualifiers: Severe hypertension, Cardiac disorder, Others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests acetazolamide, a mild diuretic drug, in young adults with obstructive sleep apnea and high blood pressure. The drug aims to improve breathing during sleep and lower blood pressure. Researchers will evaluate its effectiveness for those who struggle with current therapies. Acetazolamide has been investigated for its potential to reduce blood pressure and improve sleep-disordered breathing in patients with hypertension and obstructive sleep apnea.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like opiates, sedatives, or specific diuretics. It's best to discuss your current medications with the trial team to see if they affect your eligibility.

What evidence supports the effectiveness of the drug acetazolamide for obstructive sleep apnea?

Research shows that acetazolamide can reduce the number of apnea episodes and improve sleep quality in some patients with obstructive sleep apnea. It works by affecting blood pH and breathing control, which can help stabilize breathing during sleep. ^{1 2 3 4 5}

Is acetazolamide generally safe for humans?

Acetazolamide is generally safe for humans, but there are important safety considerations. A fatal allergic reaction (anaphylactic shock) has been reported in a person with a sulfonamide allergy, so it's crucial to check for this allergy before using acetazolamide. ^{6 7 8 9 10}

How does the drug acetazolamide differ from other treatments for obstructive sleep apnea?

Acetazolamide is unique because it works by increasing the body's drive to breathe through its effect on carbon dioxide levels, which can help stabilize breathing during sleep. It is particularly beneficial for mild cases of obstructive sleep apnea and is sometimes used in combination with other treatments for more severe cases. ^{1 3 5 11 12}

Research Team

Christopher Schmickl, MD, PhD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for young adults aged 18-50 with untreated obstructive sleep apnea (OSA), a body mass index ≤35, and abnormal blood pressure. It's not for those allergic to sulfa-drugs, using certain medications, abusing substances, or with severe health issues like uncontrolled hypertension or major organ disorders.

Inclusion Criteria

I am between 18 and 50 years old.

I have untreated sleep apnea with an AHI of 10 or more.

You have a body mass index of 35 or lower.

Exclusion Criteria

Prisoners

I am unable to understand or follow the study's procedures.

Safety concern based on MD judgment

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person), 1 visit (virtual)

Treatment Phase 1

Participants receive either acetazolamide or placebo for 2 weeks, with weekly check-ins and monitoring of sleep and cardiovascular health

2 weeks

1 visit (in-person), weekly check-ins (virtual)

Wash-out

A wash-out period between treatment phases to clear the effects of the first treatment

1-2 weeks

Treatment Phase 2

Participants receive the alternate treatment (acetazolamide or placebo) for 2 weeks, with weekly check-ins and monitoring of sleep and cardiovascular health

2 weeks

1 visit (in-person), weekly check-ins (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Optional Open-label CPAP

Participants may opt into a 2-week CPAP therapy and repeat the same activities as during the treatment phases

2 weeks

Treatment Details

Interventions

• Acetazolamide (Diuretic)

Trial Overview The study tests if acetazolamide can improve OSA and heart health in young adults. Participants will be randomly given either the drug or a placebo for two weeks each, with assessments of OSA severity and cardiovascular health after each period.

Participant Groups

Group I: Placebo, then Acetazolamide, then optional open-label CPAP-therapy Experimental Treatment 3 Interventions

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

Group II: Acetazolamide, then Placebo, then optional open-label CPAP-therapy Experimental Treatment 3 Interventions

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

Acetazolamide is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

🇪🇺 Approved in European Union as Diamox for:

• Glaucoma
• Epilepsy
• Edema

🇨🇦 Approved in Canada as Diamox for:

• Glaucoma
• Epilepsy
• Edema
• Altitude sickness

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UC San Diego; Altman Clinical and Translational Research Institute Building La Jolla, CA

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1215

Patients Recruited

1,593,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. Liu, HM., Chiang, IJ., Kuo, KN., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. Ni, YN., Holzer, RC., Thomas, RJ.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide in patients with the sleep apnoea syndrome. Tojima, H., Kunitomo, F., Kimura, H., et al.[2019]

In a study involving six patients with central sleep apnea, treatment with acetazolamide led to a significant 69% reduction in total apneas and improved sleep quality, indicating its potential therapeutic value.

The administration of acetazolamide decreased mean arterial pH from 7.42 to 7.34, suggesting that acidification may enhance respiratory rhythm during sleep, which could be a key mechanism in reducing apneas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central sleep apnea. Improvement with acetazolamide therapy. White, DP., Zwillich, CW., Pickett, CK., et al.[2013]

In a study of 20 male patients with sleep apnea, 14 showed significant improvements in apnea frequency, sleep structure, and related symptoms after treatment with acetazolamide (AZM), a carbonic anhydrase inhibitor.

The treatment led to a decrease in arterial blood pH and bicarbonate levels in the improved patients, indicating a potential mechanism of action related to metabolic changes, while the remaining 6 patients did not experience any benefits from AZM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism. Sakamoto, T., Nakazawa, Y., Hashizume, Y., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inadvertent substitution of acetohexamide for acetozolamide. Hargett, NA., Ritch, R., Mardirossian, J., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of generic acetazolamide. Ellis, PP., Price, PK., Kelmenson, R., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. Gerhards, LJ., van Arnhem, AC., Holman, ND., et al.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dorzolamide hydrochloride in the management of chronic cystoid macular edema in patients with retinitis pigmentosa. Grover, S., Fishman, GA., Fiscella, RG., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term dose response characteristics of acetazolamide in man. Friedland, BR., Mallonee, J., Anderson, DR.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide for OSA and Central Sleep Apnea: A Comprehensive Systematic Review and Meta-Analysis. Schmickl, CN., Landry, SA., Orr, JE., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome. Inoue, Y., Takata, K., Sakamoto, I., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide in patients with the sleep apnoea syndrome. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Central sleep apnea. Improvement with acetazolamide therapy. [2013]

5. Australia pubmed.ncbi.nlm.nih.gov

Effects of acetazolamide on the sleep apnea syndrome and its therapeutic mechanism. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Inadvertent substitution of acetohexamide for acetozolamide. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of generic acetazolamide. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

[Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma]. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy of dorzolamide hydrochloride in the management of chronic cystoid macular edema in patients with retinitis pigmentosa. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Short-term dose response characteristics of acetazolamide in man. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Acetazolamide for OSA and Central Sleep Apnea: A Comprehensive Systematic Review and Meta-Analysis. [2022]

12. Australia pubmed.ncbi.nlm.nih.gov

Clinical efficacy and indication of acetazolamide treatment on sleep apnea syndrome. [2013]