Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea

Summary

Obstructive sleep apnea (OSA) is a common condition in which the airway repeatedly collapses during sleep, leading to poor sleep quality and reduced oxygen levels. Hypoglossal nerve stimulation (HGNS) is an approved treatment that uses a small implanted device to stimulate the genioglossus muscle and keep the airway open. However, some patients continue to have OSA despite using HGNS. Atomoxetine and oxybutynin, "AtoOxy", is a promising pharmacologcal therapy under investigation that has been shown to activate pharyngeal muscles-in particular non-genioglossus muscles--but appears more efficacious in some patients than others.

This study will test whether the combination of AtoOxy and HGNS can further improve breathing during sleep compared to either monotherapy alone. Participants with OSA and an HGNS device will be randomized to receive, in random order: HGNS+AtoOxy, HGNS alone (plus placebo), AtoOxy alone (HGNS device off), and placebo (HGNS device off), in a cross-over trial.

The main goal is to determine whether the combined treatment reduces the number of breathing events during sleep; the primary outcome test will compare HGNS+AtoOxy versus HGNS alone. The effect of each intervention versus placebo will also be presented.

The study will also examine how individual patient characteristics influence response to treatment.

Conditions

• Obstructive Sleep Apnea
• Sleep-disordered Breathing

Interventions

OTHER

Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)

Electrical stimulation of the hypoglossal nerve using an implanted device (Inspire Medical Systems) to activate upper airway dilator muscles during sleep at prescribed therapeutic settings. Atomoxetine 80 mg administered orally at bedtime. Oxybutynin 5 mg administered orally at bedtime. Dose escalation with half-dose for initial 3 nights followed by full dose.

DEVICE

Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition

Electrical stimulation of the hypoglossal nerve using an implanted device (Inspire Medical Systems) to activate upper airway dilator muscles during sleep at prescribed therapeutic settings. Matching placebo capsules administered orally at bedtime.

DRUG

Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition

Atomoxetine 80 mg administered orally at bedtime. Oxybutynin 5 mg administered orally at bedtime. Dose escalation with half-dose for initial 3 nights followed by full dose. HGNS device off

DRUG

Placebo; placebo comparator condition

Matching placebo capsules administered orally at bedtime. HGNS device off

Sponsors & Collaborators

• Brigham and Women's Hospital

  lead OTHER

Principal Investigators

• Scott A Sands, PhD · Brigham and Women's Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

79 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-01

Primary Completion

2027-12-01

Completion

2027-12-01

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations