A Novel Pharmacological Therapy for Obstructive Sleep Apnea

Phase 2

Completed

• Conditions: Sleep Apnea
• Interventions: Drug: Atomoxetine; Drug: Oxybutynin; Drug: Placebo

• Registration Number: NCT03919955
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

A pharmacological, non-mechanical therapy for OSA that is efficacious and tolerable remains elusive. Here the investigators study the effect on sleep apnea severity of a combination of pharmacological agents (atomoxetine and oxybutynin, "AtoOxy") over a 1 month period of time. The current study will answer the following questions: Does ongoing, repeated-dose administration of atomoxetine-plus-oxybutynin (referred to as "AtoOxy") improve OSA severity, and do patients exhibit signs of symptomatic relief? Most importantly, which phenotypic subgroup of patients preferentially benefit from this intervention?

Detailed Description

Aim 1 - Effect of AtoOxy on sleep apnea severity. In a randomized controlled double-blind crossover study, 48 patients with moderate-to-severe OSA will take atomoxetine-plus-oxybutynin ("AtoOxy") versus placebo nightly for 1 month, with a 2-week washout in between. The investigators will test the hypothesis that AtoOxy reduces the Apnea-hypopnea index (primary outcome measure), and improves the following secondary outcomes:

* Nocturnal oxygenation, per "hypoxic burden of sleep apnea"

* Frequency of arousals from sleep (Arousal index)

* Self-reported sleepiness (Epworth Sleepiness Scale)

* Disease-specific quality of life (Functional Outcomes of Sleep Questionnaire, Short Form).

* Disease-specific quality of life (Sleep Apnea Quality of Life Index, Short Form)

Additional pre-specified exploratory outcome measures will be assessed, including Visual Analog Scales (Sleep Quality, Treatment Satisfaction) and additional polysomnographic measures of sleep (Stage 1 sleep, %total sleep time). Adherence and adverse events will also be carefully monitored to assess repeated-dose tolerance of the intervention.

Aim 2 - Determine which patient phenotypes respond best to AtoOxy. Patients will also take part in an additional night before initiating study medication to measure the key mechanisms causing OSA. The investigators will prospectively test the hypothesis that greater pharyngeal collapsibility determines a reduced response to therapy. They will also separately test the hypotheses that a reduced muscle responsiveness, reduced baseline muscle activation, a higher arousal threshold, and a lower loop gain will facilitate a greater response to therapy.

Study Timeline

• Study First Submitted: 2019-04-16
• Study First Submitted QC: 2019-04-16
• Study First Posted: 2019-04-18
• Study Start: 2019-09-03
• Primary Completion: 2023-09-07
• Study Completion: 2023-09-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence A: Atomoxetine and Oxybutynin, then Placebo	Atomoxetine	Sequence A: Atomoxetine and Oxybutynin, then Placebo
Sequence A: Atomoxetine and Oxybutynin, then Placebo	Oxybutynin	Sequence A: Atomoxetine and Oxybutynin, then Placebo
Sequence A: Atomoxetine and Oxybutynin, then Placebo	Placebo	Sequence A: Atomoxetine and Oxybutynin, then Placebo
Sequence B: Placebo, then Atomoxetine and Oxybutynin	Atomoxetine	Sequence B: Placebo, then Atomoxetine and Oxybutynin.
Sequence B: Placebo, then Atomoxetine and Oxybutynin	Oxybutynin	Sequence B: Placebo, then Atomoxetine and Oxybutynin.
Sequence B: Placebo, then Atomoxetine and Oxybutynin	Placebo	Sequence B: Placebo, then Atomoxetine and Oxybutynin.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Hypoxic Burden	one month	Desaturation area under curve × event frequency
Arousal index	one month	Scored EEG arousals per hour (\>3 s), % change from baseline
Epworth Sleepiness Scale	one month	Self-reported sleepiness on scale of 0-24, higher being more sleepy
Functional Outcomes of Sleep Questionnaire, Short Form	one month	Disease-specific quality of life
Sleep Apnea Quality of Life Index, Short Form	one month	Disease-specific quality of life

Trial Locations

Locations (1)

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