Endotypic Traits and Obstructive Sleep Apnea Surgery

Sponsor

University of California, Los Angeles (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05953610

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Drug: Acetazolamide 500 MG QHS Drug: Eszopiclone 3 mg QHS	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Prospective cohort study will include an anticipated 150 study participants undergoing soft palate surgery. The randomized crossover (interventional) study will include the anticipated 90 who do not achieve successful treatment of their obstructive sleep apnea with surgery.Prospective cohort study will include an anticipated 150 study participants undergoing soft palate surgery. The randomized crossover (interventional) study will include the anticipated 90 who do not achieve successful treatment of their obstructive sleep apnea with surgery.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Endotypic Traits and Obstructive Sleep Apnea Surgery

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Aug 31, 2027

Anticipated Study Completion Date :

Aug 31, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Apnea-hypopnea index [6 months]
apneas plus hypopneas per hour of sleep

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria are:

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

Exclusion criteria are:

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