Endotypic Traits and Obstructive Sleep Apnea Surgery

NCT ID: NCT05953610

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-07
• Study Completion Date: 2028-08-31

Brief Summary

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).

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.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Acetazolamide

Treatment with acetazolamide 500 mg nightly for 1 month.

Group Type: EXPERIMENTAL

Acetazolamide 500 MG QHS

Intervention Type: DRUG

Acetazolamide

Acetazolamide/Eszopiclone

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

Group Type: EXPERIMENTAL

Acetazolamide 500 MG QHS

Intervention Type: DRUG

Acetazolamide

Eszopiclone 3 mg QHS

Intervention Type: DRUG

Eszopiclone

Interventions

Acetazolamide 500 MG QHS

Acetazolamide

Intervention Type: DRUG

Eszopiclone 3 mg QHS

Eszopiclone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Eric J. Kezirian, MD, MPH

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCLA Santa Monica Medical Center

Santa Monica, California, United States

Site Status: RECRUITING

UCLA Westwood

Westwood, Los Angeles, California, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Eric J Kezirian, MD, MPH

Role: CONTACT

EKezirian@mednet.ucla.edu

32344257904242596559

Facility Contacts

Eric Kezirian, MD, MPH

Role: primary

Eric Kezirian, MD, MPH

Role: primary

Other Identifiers

R01HL160993

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1.0

Identifier Type: -

Identifier Source: org_study_id