Obstructive Sleep Apnea (OSA)
Conditions
Brief summary
Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. Some OSA patients with low arousal threshold wake up prematurely during an obstructive event and do not have time for spontaneous upper airway (UA) dilator muscle recruitment. As a consequence they are exposed to apnea and hypopnea cycling. In this protocol the investigators will test the effect of DAW2020 administered before sleep on OSA phenotype traits and OSA severity during sleep.
Detailed description
Two overnight sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnigraphy for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. DAW2020 34 mg will be given 4 hours before lights out. Subjects will sleep at least 50% of the night in the supine position. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. After the first overnight study is completed, there will be a one-week washout period prior to crossing over to the other treatment.
Interventions
DRUGPlacebo oral capsule
Placebo before sleep
DRUGDAW2020 oral capsule
DAW2020 34 mg 4 h before sleep, single night administration
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Moderate-to-severe OSA (AHI ≥ 15 events/hr)
Exclusion criteria
* All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements. * Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid). * Use of SNRIs/SSRIs. * Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition. * Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea: * Other sleep disorders: periodic limb movements (periodic limb movement arousal index \> 10/hr), narcolepsy, or parasomnias. * Hypersensitivity to the study drug (angioedema or urticaria) * Contraindications to DAW2020 * Use of medications that lengthen QTc interval * Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease * Severe claustrophobia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of DAW2020 on arousal threshold (%eupnea) | 1 night | Arousal threshold will be calculated using diaphragm EMG |
Countries
United States
Outcome results
None listed