Endotypic Traits and Obstructive Sleep Apnea Surgery

Obstructive Sleep Apnea Clinical Trial

Official title:

Endotypic Traits and Obstructive Sleep Apnea Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05953610
• Other study ID #: 1.0
• Secondary ID: R01HL160993
• Status: Recruiting
• Phase: Phase 2
• Start date: January 7, 2024
• Est. completion date: August 31, 2027

Study information

• Verified date: March 2024
• Source: University of California, Los Angeles
• Contact: Eric J Kezirian, MD, MPH
• Phone: 32344257904242596559
• Email: EKezirian[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Acetazolamide 500 MG QHS
Acetazolamide
• Eszopiclone 3 mg QHS
Eszopiclone

Locations

Country	Name	City	State
United States	UCLA Santa Monica Medical Center	Santa Monica	California
United States	UCLA Westwood	Westwood	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Vpassive	ventilation at normal ventilatory drive, as measured using software to analyze raw polysomnogram data	6 months
Other	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
Other	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
Primary	Apnea-hypopnea index	apneas plus hypopneas per hour of sleep	6 months