Acetazolamide for Obstructive Sleep Apnea

Overseen By Atqiya Aishah, 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: Unstable conditions, Glaucoma, Neuromuscular disease, others

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

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests acetazolamide to determine its effectiveness for a type of obstructive sleep apnea (OSA) known as "drive-dependent" OSA. Researchers believe acetazolamide, a medication that stimulates breathing, might reduce sleep apnea severity by stabilizing the airway during sleep. Participants will receive either acetazolamide or a placebo (a sugar pill) over three nights. This trial may suit individuals who snore, feel sleepy during the day, or have been told they stop breathing during sleep, and who have not used any sleep apnea treatment in the last two weeks. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and to measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop using any ventilatory stimulant or depressant medications, such as opioids, barbiturates, and certain others, as they may affect the results. If you are currently using the study medication, acetazolamide, you cannot participate. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

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

Research has shown that acetazolamide has been tested in people with sleep apnea and is generally well-tolerated. Studies indicate that it can help lessen the severity of sleep apnea. For example, a meta-analysis, which combines data from several studies, found that acetazolamide effectively improved sleep apnea in many cases. This suggests it could be a useful option for those with the condition.

Acetazolamide is already used for other health issues, providing some knowledge about its safety. Like any medicine, it may have side effects, but these are usually mild. Some people might feel tingling in their fingers or toes, notice changes in taste, or need to urinate more often. Always consult a healthcare provider if there are concerns about these effects. ^{1 2 3 4 5}

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

Unlike the standard treatments for obstructive sleep apnea, which often involve continuous positive airway pressure (CPAP) machines or oral appliances, acetazolamide offers a unique approach by using a medication that affects the body’s chemistry. Acetazolamide is a carbonic anhydrase inhibitor, which means it helps reduce fluid build-up and can change the pH balance in the body to improve breathing patterns. Researchers are excited because this pill-based treatment could provide a simpler, non-invasive alternative that works quickly, potentially showing results in just a few days.

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 lessen the severity of obstructive sleep apnea (OSA). One study found that acetazolamide significantly reduced the number of times breathing stopped during sleep. Another study discovered that combining acetazolamide with continuous positive airway pressure (CPAP) therapy further improved breathing during sleep. Observations indicate that the benefits of acetazolamide on sleep apnea symptoms can last for at least three months. This suggests that acetazolamide could be a promising treatment for stabilizing breathing during sleep in people with OSA. ^{2 3 6 7 8}

Who Is on the Research Team?

Dillon Gilbertson

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Scott Sands, PhD

Principal Investigator

Brigham and Women's Hospital and Harvard Medical School

Are You a Good Fit for This Trial?

This trial is for adults aged 21-80 with suspected or diagnosed obstructive sleep apnea (OSA) who haven't used OSA treatments in the last two weeks and won't start any during the study. People can't join if they're on certain medications, have allergies to sulfonamides, glaucoma, adrenal or severe kidney/liver issues, electrolyte imbalances, are pregnant/nursing, or have other conditions that might affect results.

Inclusion Criteria

I either suspect I have sleep apnea or have been diagnosed with it.

I haven't used any treatments for sleep apnea in the last 2 weeks and don't plan to start any during the study.

I am between 21 and 80 years old.

Exclusion Criteria

You are allergic to lidocaine, which is used for intramuscular electrodes and catheter procedures.

You have a medical condition that is not currently stable or well-controlled.

Contraindications for acetazolamide, including: Allergies to sulfonamides - e.g. acetazolamide, hydrochlorothiazide, furosemide, sulfasalazine, celecoxib, sumatriptan, and zonisamide; closed-angle glaucoma; adrenal insufficiency; known electrolyte or acid/base imbalance (hyponatremia, hypokalemia, hyperchloremia, metabolic acidosis, acidemia); clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2); clinically-significant liver disorders; Use of more than 500 mg/day of Aspirin, due to the potential for an interaction of acetazolamide and very high doses of Aspirin (acetylsalicylic acid, a salicylate drug); Adrenocortical insufficiency; Low sodium or potassium; hyperchloremic acidosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (virtual)

Baseline Assessment

Participants undergo a baseline routine sleep study to confirm eligibility and establish baseline characteristics

1 night

1 visit (in-person)

Treatment

Participants receive Acetazolamide or Placebo for 3 nights with a washout period of 4 days between treatments

2 weeks

2 visits (in-person)

Open-label Extension

Participants receive repeated doses of Acetazolamide for 4 weeks to assess long-term efficacy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide

Trial Overview The trial tests whether Acetazolamide can help people with a specific type of OSA by stabilizing their breathing drive compared to a placebo. Participants will be randomly assigned to receive either Acetazolamide or an inactive substance to see if there's an improvement in their condition.

How Is the Trial Designed?

Group I: Acetazolamide Experimental Treatment 1 Intervention

Acetazolamide administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2x250mg pills) for 2 nights

Group II: Placebo Placebo Group 1 Intervention

Placebo sugar pills administered for 3 nights, half-dose (1 pill) on the first night followed by full dose (2 pills) for 2 nights

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

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]

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]

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]

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]

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]

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 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]

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 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 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]

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]

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]

Citations

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

Acetazolamide for OSA and Central Sleep Apnea Based on moderate quality evidence from 26 studies,,,,,,,,,,,,,,,,,,,,,,,,,, acetazolamide reduced the AHI overall by −0.70 effect sizes (95% CI, −0.83 to −0.58 ...

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. 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 ...

4. 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 ...

5. publications.ersnet.org publications.ersnet.org/content/erj/60/suppl66/3872

Effectiveness of acetazolamide in patients with moderate ... Acetazolamide (AZT) has shown potential in the correction of central sleep apnea traits. Aim: To investigate the treatment effect of acetazolamide in patients ...

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

The effect of acetazolamide on sleep apnea at high altitude The results of this systematic review and meta-analysis including 311 cases from eight RCTs indicate that acetazolamide is effective in improving sleep apnea at ...

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

The role of acetazolamide in sleep apnea at sea level Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] −15.82, 95% CI: −21.91 to −9.74, P < .00001) in central sleep apnea (MD −22.60, 95% ...

8. 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.