Oxygen + Acetazolamide for Sleep Apnea

(SDB Trial)

Recruiting at 1 trial location

Overseen By Ruchi Rastogi, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must be taking: Opioids

Must not be taking: Tramadol, Suboxone

Disqualifiers: Morbid obesity, Cardiac disease, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether oxygen and a medication called acetazolamide can reduce breathing problems during sleep for individuals who regularly take opioids. It aims to determine if these treatments can enhance sleep quality and overall well-being. The trial tests two treatments: one involves breathing extra oxygen at night, and the other involves taking acetazolamide pills. Veterans currently using prescription opioids and experiencing sleep issues might be suitable candidates. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatments work and measuring their effectiveness in an initial group, offering participants a chance to contribute to important research.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients on tramadol and suboxone/buprenorphine. It seems you can continue other prescription opioids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that acetazolamide, a treatment under study for sleep apnea, is generally well-tolerated. A review of 26 studies found that acetazolamide reduced the severity of sleep apnea without causing serious side effects, suggesting it can be safe for managing the condition.

For hyperoxia treatment, studies have indicated that oxygen therapy can improve oxygen levels in people with sleep apnea. However, the overall safety results are limited and sometimes mixed. Discuss any concerns with a study doctor.

Both treatments have undergone testing. If questions arise about joining a trial, inquire about any risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to tackle sleep apnea. Unlike the standard of care, which often involves CPAP machines or oral appliances, acetazolamide works by affecting the body's response to carbon dioxide, potentially offering an alternative for those who struggle with current options. Meanwhile, the hyperoxia treatment aims to change how the body regulates breathing during sleep by increasing oxygen levels, which could help manage apnea episodes more effectively. These approaches are promising because they target the underlying physiological processes of sleep apnea, rather than just addressing its symptoms.

What evidence suggests that this trial's treatments could be effective for sleep apnea?

Research has shown that acetazolamide, which participants in this trial may receive, can help treat sleep apnea by stabilizing breathing during sleep. It improves blood oxygen levels and reduces the severity of sleep apnea episodes. Acetazolamide also controls breathing by reducing high loop gain, a condition where the breathing system is overly sensitive. Similarly, studies have found that oxygen therapy, another treatment option in this trial, decreases the number of sleep apnea events and improves blood oxygen levels. Both treatments could benefit people with sleep apnea, including those taking opioid medications. ^{1 3 6 7 8}

Who Is on the Research Team?

Susmita Chowdhuri, MD

Principal Investigator

John D. Dingell VA Medical Center, Detroit, MI

Are You a Good Fit for This Trial?

This trial is for veterans aged 18-89 who are on prescription opioids and may have sleep issues like apnea due to their medication. It's not open to those with severe untreated mental or physical health conditions, recent strokes or heart problems, pregnant women, very high BMI (>40), or anyone unable to consent.

Inclusion Criteria

I am a veteran prescribed opioids.

I am a veteran aged between 18 and 89.

Exclusion Criteria

I do not have severe lung, brain, liver, or kidney diseases.

I have ongoing chest pain or discomfort.

I have ongoing seizures that aren't controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Hyperoxia

Participants undergo sustained hyperoxia overnight to assess its effect on ventilatory control during sleep

2-30 days

Overnight study

Treatment - Acetazolamide

Participants receive oral acetazolamide therapy for 6 days to study its effect on cerebrovascular responsiveness to CO2

6 days

Experimental night study, experimental day study, polysomnography night study

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Hyperoxia

Trial Overview

The study tests if oxygen (hyperoxia) and a drug called acetazolamide can help reduce irregular breathing and eliminate sleep apnea in people taking chronic opioid medications. It also looks at how these treatments affect life quality, sleep, and pain levels.

How Is the Trial Designed?

Group I: Hyperoxia Experimental Treatment 1 Intervention

Determine the effect of sustained hyperoxia overnight vs room air overnight on ventilatory control during sleep, including the apneic threshold, carbon-dioxide reserve and chemosensitivity measured via pressure support ventilation (PSV) during non-rapid eye movement sleep (NREM) sleep.

Group II: Acetazolamide (ACZ) Experimental Treatment 1 Intervention

Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 6 days, While on the medication following studies will be performed - experimental night study, experimental day study, polysomnography night study (PSG).

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

John D. Dingell VA Medical Center

Collaborator

Trials

10

Recruited

1,100+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 12 male patients with stable systolic heart failure, acetazolamide significantly reduced the number of central apnea episodes from an average of 49 to 23 per hour, indicating its efficacy in treating central sleep apnea.

Acetazolamide also improved overall sleep quality and reduced daytime fatigue and unintentional daytime sleepiness, suggesting it positively impacts both sleep and daily functioning in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Javaheri, S.[2022]

Acetazolamide is effective in preventing acute mountain sickness, significantly reducing symptoms like headache and nausea, and its benefits are linked to increased arterial oxygen levels and reduced fluid retention.

While Acetazolamide can help treat established acute mountain sickness by improving oxygen levels, there is limited data on its effectiveness compared to other treatments like steroids or calcium channel blockers, and faster alternatives like Methazolamide may be more suitable in emergencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetazolamide and high altitude diseases. Bradwell, AR., Wright, AD., Winterborn, M., et al.[2013]

In a study involving 45 patients with obstructive sleep apnea (OSA), acetazolamide significantly improved oxygen levels and reduced breathing disturbances at high altitudes compared to a placebo, indicating its potential as an alternative treatment when CPAP is not used.

Acetazolamide not only enhanced nocturnal oxygen saturation and reduced apnea/hypopnea indices but also improved sleep quality and prevented high blood pressure during altitude exposure, suggesting it stimulates ventilation effectively in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. Nussbaumer-Ochsner, Y., Latshang, TD., Ulrich, S., et al.[2017]

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 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]

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/PMC8547551/

Effects of acetazolamide on control of breathing in sleep ...

Acetazolamide reduces ventilatory instability or “high loop gain” (for more details, see the “Results of Meta‐Analyses” section below Edwards et al., 2012, ...

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 improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. The drug may be of clinical benefit in patients with high loop ...

6.

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 ...

7.

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. Especially young adults with OSA are ...

8.

atsjournals.org

atsjournals.org/doi/10.1164/rccm.202109-2043OC

A Randomized Controlled Clinical Trial Exploring Safety ...

There were no serious adverse events. STM reduced the apnea–hypopnea index from 55.2 to 33.0 events/h (−41.0%) in the 400-mg group and from 61.1 ...