Clinical trial NCT05953610: Endotypic Traits and Obstructive Sleep Apnea Surgery
Official title: Endotypic Traits and Obstructive Sleep Apnea Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Obstructive Sleep Apnea
Keywords: surgery
loop gain
arousal threshold
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-07-20
Enrollment: 150
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Apnea-hypopnea index
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
measure: Pclose
timeFrame: 6 months
measure: Vpassive
timeFrame: 6 months
measure: Loop gain
timeFrame: 6 months
measure: Arousal threshold
timeFrame: 6 months
Locations:
city: Santa Monica
country: United States
facility: UCLA Santa Monica Medical Center
state: California
city: Westwood
country: United States
facility: UCLA Westwood
state: California
Study officials:
References: