Combination Drug-Therapy for Patients With Untreated Obstructive Sleep Apnea (RESCUE-Combo)
OSA, Obstructive Sleep Apnea
About this trial
This is an interventional treatment trial for OSA focused on measuring sleep, drug
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 (< 5 years)
- Prior gastric bypass surgery
- Chronic liver disease or end-stage kidney disease
- Active illicit substance use or >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).
Sites / Locations
- Altman Clinical and Translational Research Institute BuildingRecruiting
- UCSD Health - Pulmonary and Sleep ClinicRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Placebo, then Dual-Therapy, then Single/Triple-Therapy
Dual-Therapy, then Placebo, then Single/Triple-Therapy
Subjects will start with a 3-day PLACEBO regimen: Day 1: Placebo (matching Acetazolamide 250mg) at bedtime at home. Day 2: Placebo (matching Acetazolamide 500mg) at bedtime at home. Day 3: Placebo (matching Acetazolamide 500mg + Eszopiclone 2mg) at bedtime in the sleep laboratory. After a wash-out period of 4+ days, subjects will then cross-over to a 3-day EXPERIMENTAL DUAL-regimen: Day 1: Acetazolamide 250mg at bedtime at home. Day 2: Acetazolamide 500mg at bedtime at home. Day 3: Acetazolamide 500mg + Eszopiclone 2mg at bedtime in the sleep laboratory. After a wash-out period of 4+ days, subjects will then undergo an OPEN-LABEL SINGLE/TRIPLE-regimen: Day 1: Acetazolamide 250mg at bedtime at home. Day 2: Acetazolamide 500mg at bedtime at home. Day 3: Acetazolamide 500mg alone or Acetazolamide 500mg + Eszopiclone 2mg + Venlafaxine 50mg at bedtime in the sleep laboratory, if sleep apnea resolved or did not resolve with the dual regimen, respectively.
Subjects will start with a 3-day EXPERIMENTAL DUAL-regimen: Day 1: Acetazolamide 250mg at bedtime at home. Day 2: Acetazolamide 500mg at bedtime at home. Day 3: Acetazolamide 500mg + Eszopiclone 2mg at bedtime in the sleep laboratory. After a wash-out period of 4+ days, subjects will then cross-over to a 3-day PLACEBO regimen: Day 1: Placebo (matching Acetazolamide 250mg) at bedtime at home. Day 2: Placebo (matching Acetazolamide 500mg) at bedtime at home. Day 3: Placebo (matching Acetazolamide 500mg + Eszopiclone 2mg) at bedtime in the sleep laboratory. After a wash-out period of 4+ days, subjects will then undergo an OPEN-LABEL SINGLE/TRIPLE-regimen: Day 1: Acetazolamide 250mg at bedtime at home. Day 2: Acetazolamide 500mg at bedtime at home. Day 3: Acetazolamide 500mg alone or Acetazolamide 500mg + Eszopiclone 2mg + Venlafaxine 50mg at bedtime in the sleep laboratory, if sleep apnea resolved or did not resolve with the dual regimen, respectively.