Combination Pharmacological Interventions for Multiple Mechanisms of Obstructive Sleep Apnea

Phase 1

Completed

• Conditions: Sleep Apnea
• Interventions: Drug: SAS0421a; Drug: SAS0421c; Drug: placebo; Drug: SAS0421b

• Registration Number: NCT03892772
• Lead Sponsor: Brigham and Women's Hospital

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).

Study Timeline

• Study Start: 2019-01-14
• Study First Submitted: 2019-03-26
• Study First Submitted QC: 2019-03-26
• Study First Posted: 2019-03-27
• Primary Completion: 2021-07-03
• Study Completion: 2021-07-03
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-28
• Last Update Posted: 2022-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SAS0421a, SAS0421b and SAS0421c	SAS0421a	Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
SAS0421a, SAS0421b and SAS0421c	SAS0421b	Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
SAS0421c	SAS0421c	Participants will take SAS0421c for 3 days. Half doses will be given on the first night.
SAS0421a and SAS0421b	SAS0421b	Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
SAS0421a, SAS0421b and SAS0421c	SAS0421c	Participants will take SAS0421a, SAS0421b and SAS0421c for 3 days. Half doses will be given on the first night.
SAS0421a and SAS0421b	SAS0421a	Participants will take SAS0421a and SAS0421b for 3 days. Half doses will be given on the first night.
Placebo	placebo	Participants will take placebos for 3 days.

Primary Outcome Measures

Name	Time	Method
Apnea-hypopnea index [AHI]	3 days	Apneas and hypopneas per hour (3% desat and/or arousal), % change from baseline

Secondary Outcome Measures

Name	Time	Method
Arousal Index	3 days	Number of arousals per hour (\>=3-sec), % change from baseline
Hypoxic Burden	3 days	Desaturation area under curve × event frequency
Visual Analog Scale for Sleep Quality	3 days	Sleep Quality 0-10 scale, 0 worst sleep quality, 10 best sleep quality
Visual Analog Scale for Waking Unrefreshed	3 days	Waking Unrefreshed 0-10 scale, 0 extremely refreshed, 10 extremely unrefreshed

Trial Locations

Locations (2)

Monash University; 🇦🇺 Clayton, Victoria, Australia

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States