Endotypic Traits and Obstructive Sleep Apnea Surgery

This study will examine factors associated with outcomes after soft palate surgery and medications (acetazolamide, eszopiclone) that may treat other potential causes of obstructive sleep apnea (loop gain, arousal threshold).

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Acetazolamide 500 MG QHS; Drug: Eszopiclone 3 mg QHS

Detailed Description

This is a prospective cohort (observational) study of 150 participants with moderate to severe obstructive sleep apnea (OSA) unable to tolerate positive airway pressure who are undergoing drug-induced sleep endoscopy (DISE), including measurement of upper airway closing pressure (Pclose), and tissue-repositioning soft palate surgery. Before and 6 months after surgery, the investigators will measure OSA severity (apnea-hypopnea index) with sleep studies (polysomnograms). Using a recently-validated polysomnography-based signal processing algorithm, the investigators will systematically assess the underlying mechanisms of OSA (traits) and airflow shape (consistent with palate obstruction). The expected 90 participants without resolution of OSA after surgery (surgery failures) will participate in an experimental randomized crossover study of acetazolamide (1 month) and acetazolamide/eszopiclone combination (1 month). Polysomnograms will be performed with each treatment, with algorithm-based determination of traits.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eric J Kezirian, MD, MPH; Phone Number: 32344257904242596559; Email: EKezirian@mednet.ucla.edu

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90401
      • Recruiting
      • UCLA Santa Monica Medical Center
      • Principal Investigator: Eric Kezirian, MD, MPH
      • Contact: Eric Kezirian, MD, MPH
    • Westwood, California, United States, 90095
      • Not yet recruiting
      • UCLA Westwood
      • Principal Investigator: Eric Kezirian, MD, MPH
      • Contact: Eric Kezirian, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria are:

1. age ≥21 years;
2. moderate to severe OSA (obstructive AHI ≥ 15 events/hour);
3. central/mixed apnea index <5 events/hour;
4. intolerance of positive airway pressure (defined as use < 2 hours/night at least 5 nights/week);
5. intolerance or poor candidate for oral appliance;
6. participant has provided informed consent for palate surgery as part of their standard of care;
7. tonsil size 0-2+ (without markedly enlarged tonsils that have high surgical success rates);
8. DISE without evidence of complete tongue-related obstruction (reflecting poorer results with isolated palate surgery);
9. medications stable for ≥2 months;
10. body mass index <35 kg/m2;
11. absence of uncontrolled nasal obstruction;
12. no prior pharyngeal surgery other than tonsillectomy;
13. no neurologic, cardiac or pulmonary disorders;
14. absence of psychiatric disorder except for treated depression or mild anxiety;
15. no co-existing sleep disorder, such as narcolepsy, chronic insomnia, or restless legs syndrome;
16. no use of hypnotics, anxiolytics, stimulants, or sedating antidepressants;
17. no near-miss or prior motor vehicle crash due to sleepiness in past 12 months; and
18. <3 caffeinated beverages daily.

Exclusion criteria are:

1. history of allergic reaction to either of the study drugs;
2. subjects with prior serious allergic reaction (such as Stevens-Johnson syndrome) to sulfonamides;
3. subjects with a history of hypersensitivity to either of the two study drugs;
4. subjects who are on high-dose aspirin therapy due to risk of severe metabolic acidosis;
5. subjects with severe kidney disease or severe liver disease;
6. subjects with a history of electrolyte imbalance or adrenal insufficiency (due to risks related to acetazolamide);
7. subjects on ketoconazole or other strong CYP3A4 inhibitors (these will increase eszopiclone blood levels);
8. pregnancy; and
9. alcohol or substance abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetazolamide; Treatment with acetazolamide 500 mg nightly for 1 month.	Drug: Acetazolamide 500 MG QHS; Acetazolamide
Experimental: Acetazolamide/Eszopiclone; Treatment with acetazolamide 500 mg and eszopiclone 3 mg nightly for 1 month.	Drug: Acetazolamide 500 MG QHS; Acetazolamide; Drug: Eszopiclone 3 mg QHS; Eszopiclone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea-hypopnea index	apneas plus hypopneas per hour of sleep	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pclose	upper airway closing pressure, as measured with administration of positive airway pressure therapy and observation of airway dimensions with flexible fiberoptic endoscopy	6 months
Vpassive	ventilation at normal ventilatory drive, as measured using software to analyze raw polysomnogram data	6 months
Loop gain	ventilatory drive response to a 1 cycle/min reduction in ventilation (ventilatory control), as measured using software to analyze raw polysomnogram data	6 months
Arousal threshold	median ventilatory drive immediately preceding scored EEG arousals (propensity to wake up), as measured using software to analyze raw polysomnogram data	6 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: surgery; loop gain; arousal threshold
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Central Nervous System Depressants; Hypnotics and Sedatives; Diuretics; Natriuretic Agents; Anticonvulsants; Carbonic Anhydrase Inhibitors; Eszopiclone; Acetazolamide
• Other Study ID Numbers: 1.0; R01HL160993 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No