Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea
Overview
- Phase
- Phase 1
- Intervention
- SAS0421b
- Conditions
- Sleep Apnea
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 23
- Locations
- 2
- Primary Endpoint
- Apnea-hypopnea index [AHI]
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Currently, there is no pharmacological intervention for OSA that targets multiple pathophysiological deficits in combination. Here the investigators study the effect on sleep apnea severity of combinations of pharmacological agents that stimulate the pharyngeal muscles, stabilize ventilatory control, and increase the arousal threshold.
Detailed Description
The primary goal of the current study is to determine the effect of combination therapy targeting phenotypic traits on OSA severity. Specifically, the investigators will assess the effect of combination pharmacological therapy on OSA severity as measured by the apnea-hypopnea index and the arousal index (co-primary outcome variables). The investigators will also estimate the effects of the interventions on the physiological traits responsible for OSA using polysomnography, namely: * Pharyngeal anatomy and its propensity towards collapse * The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation) * Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep). * Stability of the ventilatory control system feedback loop (i.e. loop gain). Baseline traits will be used to examine whether patient characteristics influence the responses to each combination of interventions (i.e. muscles, muscles plus loop gain, muscles plus arousal threshold).
Investigators
Scott Aaron Sands
Assistant Professor of Medicine
Brigham and Women's Hospital
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
SAS0421a, SAS0421b and SAS0421c
Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
Intervention: SAS0421b
SAS0421a, SAS0421b and SAS0421c
Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
Intervention: SAS0421a
SAS0421a, SAS0421b and SAS0421c
Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
Intervention: SAS0421c
SAS0421a and SAS0421b
Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
Intervention: SAS0421a
SAS0421a and SAS0421b
Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
Intervention: SAS0421b
SAS0421c
Participants will take SAS0421c for 3 days. Half doses will be given on the first night.
Intervention: SAS0421c
Placebo
Participants will take placebos for 3 days.
Intervention: placebo
Outcomes
Primary Outcomes
Apnea-hypopnea index [AHI]
Time Frame: 3 days
Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline
Secondary Outcomes
- Arousal Index(3 days)
- Hypoxic Burden(3 days)
- Visual Analog Scale for Sleep Quality(3 days)
- Visual Analog Scale for Waking Unrefreshed(3 days)