Surgery + Medication for Obstructive Sleep Apnea

Recruiting at 2 trial locations

Overseen By Eric J Kezirian, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Hypnotics, Anxiolytics, Stimulants, others

Disqualifiers: Severe kidney, Severe liver, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 months

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of soft palate surgery and medications can effectively treat obstructive sleep apnea (OSA). Researchers are examining how surgery on the soft palate, combined with the drugs acetazolamide (a diuretic) and eszopiclone (a sleep aid), might improve breathing control and reduce sleep arousal. The trial specifically targets individuals with moderate to severe OSA who struggle with CPAP machines and have agreed to soft palate surgery as part of their care. It suits those who find CPAP machines uncomfortable and have already considered surgery. Participants should not have other sleep disorders, significant nasal blockages, or recent sleepiness-related accidents. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that your medications have been stable for at least 2 months, and you cannot use hypnotics, anxiolytics, stimulants, or sedating antidepressants. If you are on these medications, you may need to stop them before participating.

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

In earlier studies, acetazolamide has shown promise in helping people with sleep apnea by reducing the frequency of breathing interruptions during sleep. Research shows it can lower blood pressure and improve sleep quality. Most people tolerate it well, experiencing no major side effects.

When combined with eszopiclone, research suggests this pair can effectively reduce the severity of sleep apnea. The combination is well-tolerated for short-term use, with improvements in sleep patterns.

Overall, both treatments have proven safe for many people. While some side effects may occur, they are usually not serious. It's always advisable to consult a healthcare provider with any questions or concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of acetazolamide and eszopiclone for obstructive sleep apnea because it offers a new approach by potentially enhancing sleep quality while targeting the underlying issues of apnea. Unlike standard treatments like CPAP machines or lifestyle changes, acetazolamide works by adjusting the body's acid-base balance, which can help improve breathing patterns during sleep. Eszopiclone, on the other hand, is a sleep aid that may help patients achieve deeper, more restful sleep. This dual-action approach could make it easier for patients to manage their condition with medications rather than solely relying on mechanical devices.

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

Research has shown that acetazolamide, which participants in this trial may receive, can improve obstructive sleep apnea (OSA) by reducing the frequency of breathing interruptions during sleep. One study found that acetazolamide decreased these interruptions by 16 times per hour and increased oxygen levels during sleep. Another treatment option in this trial is the combination of acetazolamide with eszopiclone. Studies suggest that this combination leads to even greater improvement in sleep apnea symptoms. This combination was well tolerated and reduced the severity of OSA. These findings suggest that these treatments could effectively manage obstructive sleep apnea. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 21 with moderate to severe obstructive sleep apnea who haven't had much success with standard treatments and have a BMI under 35. Candidates should not have other major health issues, psychiatric disorders (except treated depression or mild anxiety), or be taking certain medications that affect sleep.

Inclusion Criteria

I have no psychiatric conditions, except possibly treated depression or mild anxiety.

My sleep study shows no complete blockage caused by my tongue.

I am 21 years old or older.

Exclusion Criteria

I am not taking ketoconazole or strong CYP3A4 inhibitors.

I have had issues with electrolyte imbalance or adrenal problems.

You have problems with drinking alcohol or using drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Assessment

Participants undergo drug-induced sleep endoscopy and tissue-repositioning soft palate surgery. OSA severity is measured before surgery.

6 months

Multiple visits for surgery and assessments

Treatment

Participants with unresolved OSA after surgery receive acetazolamide for 1 month, followed by acetazolamide/eszopiclone combination for another month.

2 months

Polysomnograms performed with each treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of OSA severity and other traits.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acetazolamide
• Eszopiclone
• Soft Palate Surgery

Trial Overview The study is testing the effectiveness of two drugs, Acetazolamide and Eszopiclone, in combination with soft palate surgery to treat obstructive sleep apnea. It aims to see if these can address underlying causes like loop gain and arousal threshold.

How Is the Trial Designed?

Group I: Acetazolamide/Eszopiclone Experimental Treatment 2 Interventions

Treatment with acetazolamide 500 mg and eszopiclone 3 mg nightly for 1 month.

Group II: Acetazolamide Experimental Treatment 1 Intervention

Treatment with acetazolamide 500 mg nightly for 1 month.

Soft Palate Surgery is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Soft Palate Surgery for:

• Obstructive Sleep Apnea
• Snoring

Approved in European Union as Soft Palate Surgery for:

• Obstructive Sleep Apnea
• Snoring

Approved in Canada as Soft Palate Surgery for:

• Obstructive Sleep Apnea
• Snoring

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The modified technique of uvulopalatopharyngoplasty combined with expansion sphincteroplasty focuses on reconstructive methods to improve the airway, which is crucial for the success of sleep apnea surgery.

This approach aims to enhance the positioning and tension of the palatopharyngeus muscle, thereby effectively opening the retropalatal airway and reducing tension during closure, which may lead to better surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palatopharyngoplasty and Palatal Anatomy and Phenotypes for Treatment of Sleep Apnea in the Twenty-first Century. Puccia, R., Woodson, BT.[2022]

In a study of 20 patients with mild to moderate obstructive sleep apnea (OSA), uvulopalatopharyngoplasty (UPPP) resulted in a significant reduction of the respiratory disturbance index (RDI), with 75% of patients showing at least a 50% reduction 4-6 months post-surgery.

One year after the procedure, 60% of patients maintained a 50% reduction in RDI, although there was a slight increase in RDI from the initial post-operative results, highlighting the need for ongoing monitoring to address potential deterioration in outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The evaluation of the effectiveness of uvulopalatopharyngoplasy in the treatment of selected patients with mild to moderate obstructive sleep apnoea--one year of postoperative follow up]. Walenczak, I., Sieśkiewicz, A., Rogowski, M., et al.[2007]

In a study of 54 patients undergoing uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea syndrome (OSAS), the strength of the anterior portion of the tongue was significantly greater in patients who experienced surgical success compared to those who did not.

Other factors like body mass index (BMI), preoperative apnea-hypopnea index (AHI), and cephalometric measurements did not influence the success of the surgery, highlighting the importance of muscle function in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of uvulopalatopharyngoplasty success in the treatment of obstructive sleep apnea syndrome. Braga, A., Grechi, TH., Eckeli, A., et al.[2022]

In a large study of 3,130 veterans undergoing uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea, the serious nonfatal complication rate was found to be 1.5%, indicating a relatively low risk of complications associated with this common surgical procedure.

The 30-day mortality rate after UPPP was very low at 0.2%, suggesting that the surgery is generally safe for patients, with no significant impact from the year of surgery or patient age on these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of serious complications after uvulopalatopharyngoplasty. Kezirian, EJ., Weaver, EM., Yueh, B., et al.[2023]

A new conservative surgical technique for treating obstructive sleep apnea and snoring shows promise by minimizing postoperative pain and maintaining a normal appearance of the soft palate, unlike traditional uvulopalatopharyngoplasty (UPPP).

In a small study of eight patients, including those with obesity and hypertension, the new technique resulted in less postoperative discomfort compared to UPPP, which is known for causing significant pain and other complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapalatine resection (IPR) in the treatment of sleep apnea and snoring. Crestinu, JM.[2019]

Uvulopalatopharyngoplasty is a generally safe and effective surgical option for treating obstructive sleep apnea and severe snoring, with most complications manageable through proper surgical techniques.

To enhance surgical effectiveness, it is crucial to focus on widening the nasopharynx and removing tissue deeply in the inferior tonsillar poles while minimizing soft palate shortening and avoiding excessive resection of the posterior pillars.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operative techniques of uvulopalatopharyngoplasty. Fairbanks, DN.[2022]

Uvulopalatopharyngoplasty (UPPP) is the most common surgery for sleep apnea syndrome, but it only shows successful results in about 50% of cases, indicating a need for better patient selection and management.

Alternative surgical options, such as retro-tongue-base-pharynx (RTBP) surgery and maxillomandibular advancement, may provide more effective solutions for patients with airway obstructions beyond the palatopharynx.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical alternatives to uvulopalatopharyngoplasty in sleep apnea syndrome. Crampette, L., Carlander, B., Mondain, M., et al.[2019]

In a study of 345 patients who underwent uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea, the most common complication was oxyhemoglobin desaturation, occurring in 12.8% of cases, indicating a relatively low incidence of complications compared to historical data.

Patients with higher apnea-hypopnea index (AHI) scores and higher body mass index (BMI) were at greater risk for complications, suggesting that those with AHI ≥ 22 and BMI > 30 kg/m² should be monitored overnight after surgery for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence of early post-operative complications following uvulopalatopharyngoplasty: identification of predictive risk factors. Kandasamy, T., Wright, ED., Fuller, J., et al.[2023]

In a study of 40 patients undergoing uvulopalatopharyngoplasty (UPPP), the use of positive end-expiratory pressure (PEEP) ventilation significantly improved vascular endothelial cell function by decreasing levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) after surgery.

Patients receiving PEEP ventilation also showed increased nitric oxide (NO) levels, indicating enhanced endothelial function, compared to those who did not receive PEEP, suggesting that this ventilation strategy may help reduce cardiovascular risks during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of positive end-expiratory pressure ventilation on plasma nitric oxide, endothelin-1 and vascular celladhesion molecule-1 levels in patients undergoing uvulopalatopharyngoplasty. Du, YR., Shi, HX., Yu, JS., et al.[2021]

Transpalatal advancement pharyngoplasty, a modified surgical technique for obstructive sleep apnea (OSA), showed promising results in increasing airway size and reducing respiratory disturbance index (RDI) in patients, with a significant decrease from 73.3 to 25.1 events per hour across all 11 patients studied.

Of the 6 patients who underwent this procedure alone, 67% achieved successful outcomes, defined as an RDI of less than 20 events per hour, indicating that this method may be a viable alternative to traditional Uvulopalatopharyngoplasty (UPPP) for select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transpalatal advancement pharyngoplasty for obstructive sleep apnea. Woodson, BT., Toohill, RJ.[2004]

Traditional uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea can lead to side effects like foreign body sensation and chronic discomfort, with rare complications such as nasopharyngeal stenosis.

Modified UPPP techniques aim to reduce these side effects by preserving more soft palate tissues and using less invasive methods, potentially improving patient comfort while maintaining effectiveness in treating OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue-Sparing Uvulopalatopharyngoplasty for OSA: Conservative, Compassionate and Possibly just as Effective. Camacho, M., Certal, V., Modi, R., et al.[2020]

In a study of 22 mostly obese males with obstructive sleep apnea (OSA), Uvulopalatopharyngoplasty (UPPP) was found to be ineffective, with only 13.6% of patients achieving successful outcomes (AHI/RDI ≤ 10) after surgery.

Most patients continued to experience severe OSA post-surgery, with a mean apnea-hypopnea index (AHI) of 53 and significant daytime sleepiness, indicating that UPPP may not be a suitable treatment for obese individuals with severe OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Failure of uvulopalatopharyngoplasty (UPPP) in severe obstructive sleep apnoea (OSA)]. Pływaczewski, R., Bednarek, M., Jonczak, L., et al.[2012]

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. 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 ...

3. 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 ...

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. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.9306

Acetazolamide for central sleep apnea: teaching an old drug ... Acetazolamide reduced the apnea-hypopnea index (AHI) by a mean difference of 16 events/h for the 14 studies overall. However, patients with CSA ...

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.