Phase 2
N=20
Combination Drug-Therapy for Patients With Untreated Obstructive Sleep Apnea
OSA · Obstructive Sleep Apnea
Bottom Line
View on ClinicalTrials.gov: NCT04639193 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
May 2024
Primary outcome: Primary: Apnea Hypopnea Index (AHI) — 17.1; 32.7; 26; 23.6 events/hour of sleep
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Acetazolamide (Drug); Eszopiclone (Drug); Placebo (Drug); Venlafaxine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of California, San Diego
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Apnea Hypopnea Index (AHI) |
17.1; 32.7; 26; 23.6; 37.4; 25.8 | — |
| SECONDARY SpO2 Nadir |
83.5; 84; 86 | — |
| SECONDARY Pathophysiological Traits: Vpassive, Vactive, Arousal Threshold |
69.5; 67.4; 70.4; 96.2; 92.1; 94.4 | — |
| SECONDARY Pathophysiological Trait: Loop Gain |
0.54; 0.57; 0.49 | — |
| SECONDARY Percent Responders |
5; 0; 4; 1; 1; 4 | — |
| SECONDARY Blood Pressure |
112.5; 116.5; 116; 72; 74; 70.5 | — |
| SECONDARY Subjective Sleepiness: Stanford Sleepiness Scale (SSS) |
2; 2; 2 | — |
| SECONDARY Sleep Quality: PROMIS (Patient-Reported Outcomes Measurement Information System) Sleep Disturbance |
53; 53.9; 53 | — |
| SECONDARY Psychomotor Vigilance: Response Speed |
3; 3.1; 2.9 | — |
| SECONDARY Psychomotor Vigilance: Lapses |
3; 3; 5 | — |
Summary
Obstructive sleep apnea (OSA) is common and associated with many adverse health consequences, but many patients are unable to tolerate standard therapies such as continuous positive airway pressure (CPAP) and thus remain untreated. Single-drug therapies have shown promising results in treating sleep apnea, but on average patients have only experienced partial relief. Multi-drug therapy may offer a more effective treatment approach. The goal of this study is to test the effect of combination therapy with three FDA-approved drugs (Diamox [acetazolamide], Lunesta [eszopiclone] +/- Effexor [venlafaxine]) on OSA severity and physiology.
Eligibility Criteria
Inclusion Criteria
- BMI 18-40 kg/m2
- Untreated Moderate or Severe OSA (AHI during supine NREM sleep >15/h) with a fraction of hypopneas >25% of all events
Exclusion Criteria
- Pregnancy
- Breastfeeding
- Prisoners
- Adherent with effective therapy for OSA
- Other known untreated sleep fragmenting disorder, such as periodic limb movement disorder, or narcolepsy
- Inability to sleep supine for overnight sleep studies
- Circadian rhythm disorder
- Unrevascularized coronary artery disease, angina, prior heart attack or stroke, congestive heart failure
- Uncontrolled hypertension (systolic blood pressure >160mmHg, diastolic blood pressure >95mmHg)
- Presence of tracheostomy
- Hospitalization within the past 90 days
- Prior peptic ulcer disease, esophageal varices, or gastrointestinal bleeding ( 2 oz daily alcohol use (i.e. >2 12 oz bottles of beers, >2 5 oz glasses of wine, >2 1.5 oz glasses of hard liquor such as spirits, gin, whiskey, etc.)
- Psychiatric disease, other than well controlled depression/anxiety
- Cognitive impairment, inability to provide consent, or inability to complete research procedures (e.g. questionnaires that are only available/validated in English)
- Chronically using study drugs or drugs with similar pharmacodynamic effects (acetazolamide - carbonic anhydrase inhibitors, eszopiclone - benzodiazepine receptor agonists, venlafaxine - serotonin/norepinephrine reuptake inhibitors and other antidepressants)
- Regular use of medications known to affect control of breathing (opioids, benzodiazepines, theophylline)
- Contraindications to taking study drugs, including allergies to any of the drugs or sulfa allergy; concomitant use of antidepressants, opioids, sedatives/hypnotics, thiazide diuretics or angiotensin-receptor blockers; or severe nocturnal hypoxia (SpO2 nadir <70% on diagnostic sleep study).
Data sourced from ClinicalTrials.gov (NCT04639193). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.