NCT03919955

A Novel Pharmacological Therapy for Obstructive Sleep Apnea

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 117 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Sleep Apnea

Interventions

Type	Name	Description
DRUG	Atomoxetine	Atomoxetine 80 mg, per mouth, before bed. Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.
DRUG	Oxybutynin	Oxybutynin 5 mg, per mouth, before bed. Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.
DRUG	Placebo	Placebo, per mouth, before bed.Participants will take the intervention nightly for one month. Half doses will be given on the first three nights.

Timeline

• Start date: 2019-09-03
• Primary completion: 2023-09-07
• Completion: 2023-09-07
• First posted: 2019-04-18
• Last updated: 2025-12-23
• Results posted: 2025-12-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study