Acetazolamide for Obstructive Sleep Apnea

(RemmOSA Trial)

Overseen By Ludovico Messineo, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Opioids, Barbiturates, Theophylline, others

Disqualifiers: Uncontrolled conditions, Neuromuscular disease, Heart failure, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 nights

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the medication acetazolamide can help individuals with REM-related obstructive sleep apnea (OSA), a condition that interrupts breathing during sleep. Researchers aim to determine if this medication can reduce breathing problems during REM sleep, which often involves more severe OSA episodes. Participants will receive either acetazolamide (a diuretic medication) or a placebo before bedtime for a few nights to observe its effects. The study seeks individuals diagnosed with REM OSA, who experience REM sleep for more than 10 minutes, and are not currently using CPAP machines. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that are expected to stimulate or depress breathing, such as opioids or barbiturates. If you are currently using the medications being studied, you will also need to stop those.

Is there any evidence suggesting that Acetazolamide is likely to be safe for humans?

Research has shown that acetazolamide has been studied for various conditions, including sleep apnea. In these studies, most patients tolerated acetazolamide well. For instance, one study found that acetazolamide helped reduce breathing problems during sleep and lowered blood pressure in people with sleep apnea and high blood pressure. Another study demonstrated that acetazolamide effectively decreased the number of breathing interruptions during sleep for at least three months.

While these findings are encouraging for safety, acetazolamide is already approved for other uses, such as treating altitude sickness and certain eye conditions. This approval suggests the treatment is generally safe, but individual experiences can differ. Always consult healthcare providers for personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea?

Acetazolamide is unique because it offers a fresh approach to treating obstructive sleep apnea by targeting carbonic anhydrase, an enzyme that helps regulate breathing during sleep. Unlike standard treatments like CPAP machines, which mechanically keep airways open, or oral appliances that reposition the jaw, Acetazolamide works at a biochemical level to enhance respiratory drive. Researchers are excited about this treatment because it has the potential to improve breathing patterns during sleep without the need for external devices, making it a more comfortable option for patients.

What evidence suggests that Acetazolamide might be an effective treatment for obstructive sleep apnea?

Research has shown that acetazolamide, which participants in this trial may receive, can help treat obstructive sleep apnea (OSA). Studies have found it improves oxygen levels during sleep. For instance, one study noted that acetazolamide raised the lowest oxygen level by 4.4% in people with sleep apnea. It also lowers the apnea-hypopnea index (AHI), which measures the severity of sleep apnea, during non-REM sleep. Moreover, its positive effects on sleep apnea can last for at least three months. These findings suggest acetazolamide may improve breathing and oxygen levels during sleep for those with OSA. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with REM sleep apnea who haven't used CPAP for over a week. Participants should have more severe symptoms during REM than non-REM sleep and not be on any medication that affects breathing or have conditions like uncontrolled medical issues, major neurological disorders, heart failure, respiratory diseases other than sleep apnea, or be pregnant.

Inclusion Criteria

REM duration>10 minutes

Not using CPAP (>1 week)

Diagnosed REM OSA (per baseline screening: REM AHI/nREM AHI≥2)

Exclusion Criteria

I do not have any uncontrolled medical conditions.

I am currently taking the medication being studied.

I am not taking medications that affect my breathing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Baseline home sleep test to assess the presence of OSA and REM OSA

1 night

1 visit (home)

Treatment

Participants undergo two overnight, in-lab sleep studies with Acetazolamide and placebo

2 nights

2 visits (in-lab)

Washout

Four day washout period between treatment nights

4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Placebo oral capsule

Trial Overview The study tests if Acetazolamide can help with REM-related obstructive sleep apnea by improving muscle activity in the airway and breathing drive during sleep. It's compared to a placebo capsule to see if there's a real effect.

How Is the Trial Designed?

Group I: Acetazolamide Active Control 1 Intervention

Acetazolamide 250 mg before bedtime 3 nights before the study, Acetazolamide 500 mg before bedtime for 2 nights before the study (inclusive)

Group II: Placebo Placebo Group 1 Intervention

Placebo capsule before bedtime for 3 nights before the studies (inclusive)

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

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

In a study involving five patients with retinitis pigmentosa and chronic cystoid macular edema, oral acetazolamide was found to be more effective than topical dorzolamide in improving visual acuity and managing macular edema.

While dorzolamide showed some subjective improvements in visual function and slight reductions in macular edema for some patients, it did not lead to measurable improvements in visual acuity, unlike acetazolamide which improved visual acuity in three out of five patients.

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]

In a study of nine patients with obstructive sleep apnoea, acetazolamide (250 mg/day) significantly reduced the apnoea index from 25.0 to 18.1 episodes per hour and decreased the total time of arterial oxygen desaturation during sleep.

Acetazolamide appears to improve symptoms of daytime hypersomnolence in some patients and enhances ventilatory control by increasing the body's response to carbon dioxide, suggesting it may be beneficial for mild cases of obstructive sleep apnoea, although it does not completely eliminate apnoea.

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 of 75 patients with sleep apnea syndrome, acetazolamide treatment significantly improved respiratory disorder variables, but only 45.3% of patients showed a meaningful reduction in their apnea hypopnea index (AHI).

Acetazolamide is most effective for mild cases of sleep apnea without obesity, while severe cases may benefit more from a combination of acetazolamide and uvulopalatopharyngoplasty.

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]

Acetazolamide significantly improves sleep apnea at high altitudes by reducing the Apnea-Hypopnea Index (AHI) and increasing nocturnal oxygenation, particularly in healthy trekkers compared to those with obstructive sleep apnea (OSA).

A daily dose of 250 mg of acetazolamide may be as effective as higher doses for healthy individuals, suggesting a potential optimal therapeutic dose for treating sleep apnea in high-altitude conditions.

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]

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]

There were three cases where acetohexamide was mistakenly given instead of acetazolamide due to their similar appearance and names, highlighting a significant risk for medication errors.

One patient experienced a severe hypoglycemic reaction leading to head trauma and confusion, which required emergency hospitalization, demonstrating the potential dangers of such medication mix-ups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

A 66-year-old woman experienced irreversible anaphylactic shock and severe pulmonary edema after being prescribed acetazolamide for glaucoma, likely due to a cross-reaction with her known sulphonamide allergy.

This case highlights the critical importance of screening for sulphonamide allergies before prescribing acetazolamide, as such allergies should be considered a contraindication due to the chemical similarities between the two drugs.

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]

In a study involving nine patients with ocular hypertension, acetazolamide effectively reduced intraocular pressure (IOP) by 30% to 35%, with the most significant response observed at a 63 mg dose, which lowered IOP by an average of 8.2 mm Hg.

Higher doses of acetazolamide (up to 500 mg) did not produce a proportionally greater reduction in IOP, indicating that a 63 mg dose is sufficient for effective treatment, as it achieves similar results to higher doses without the need for increased plasma levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Acetazolamide significantly reduced the apnea-hypopnea index (AHI) by approximately 37.7% in patients with both obstructive sleep apnea (OSA) and central sleep apnea (CSA), based on a meta-analysis of 28 studies involving 1,095 participants.

The effectiveness of acetazolamide was similar for both OSA and CSA, with higher doses (up to 500 mg/day) leading to greater reductions in AHI, indicating its potential as a treatment option for both types of sleep apnea.

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]

Generic acetazolamide and brand-name acetazolamide (Diamox) have equivalent effects on lowering intraocular pressure and achieve comparable blood levels after a single dose.

The cost of generic acetazolamide is 37% lower than that of the brand-name version, and food intake does not affect the absorption of acetazolamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of generic acetazolamide. Ellis, PP., Price, PK., Kelmenson, R., 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]

Acetazolamide (AZT) significantly improved sleep apnea symptoms in patients with high loop gain sleep apnea (HLGSA) both acutely and over a 3-month period, showing a notable reduction in the apnea hypopnea index (AHI) and breathing-related arousal index when combined with positive airway pressure (PAP) therapy.

The study involved 231 participants, with a strong predictor for treatment response being the non-rapid eye movement (NREM) AHI, indicating that AZT is a well-tolerated and effective option for managing HLGSA.

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7768933/

Acetazolamide for OSA and Central Sleep Apnea Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I2 = 63%; no evidence of effect modification; very low QoE) and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11789965/

Comparing standard treatment of moderate to severe ... In our study, the CPAP plus acetazolamide group demonstrated a significant reduction in both overall AHI and non-REM AHI compared to the CPAP ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945723001405

Acute and long-term effects of acetazolamide in presumed ... The effect of acetazolamide in reducing residual sleep apnea lasts at least 3 months. •. The apnea-hypopnea index during non-rapid eye movement sleep is a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05804084

Study Details | NCT05804084 | Patient-centered and ... 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 ...

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.9116

The role of acetazolamide in sleep apnea at sea level Acetazolamide reduces blood pressure and sleep-disordered breathing in patients with hypertension and obstructive sleep apnea: a randomized controlled trial.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05616260

Acetazolamide for Obstructive Sleep Apnea to Improve ... Recent data suggest, that acetazolamide may help OSA patients to not choke in their sleep and lower their blood pressure.

7. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.6968

Acetazolamide Reduces Blood Pressure and Sleep ... AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5941979/

The effect of acetazolamide on sleep apnea at high altitude Acetazolamide is more beneficial in healthy participants than in OSA patients, and a 250 mg daily dose may be as effective as higher daily doses for healthy ...