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

ConditionsObstructive Sleep Apnea Sleep-disordered Breathing

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-79

SponsorBrigham and Women's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Ages 18 - 79 years

Diagnosed OSA

Implantation of a hypoglossal nerve stimulation device (HGNS, Inspire Medical) or scheduled for implantation (implantation required for randomization)

Willingness to withhold HGNS while testing therapies (up to 6 weeks with HGNS off [with/without pharmacotherapy] to assess benefits of HGNS therapy).

Disqualifiers

Any uncontrolled medical condition

Current use of the medications under investigation.

Issues relating to short-term withdrawal of HGNS therapy

Excluded: Occupational driving (truck drivers, fork-lift operation, taxi/uber drivers)

Trial design

Design model

Crossover

Treatments tested in this trial

Combination device and drug: Unilateral hypoglossal nerve stimulation & atomoxetine-plus-oxybutynin (HGNS+AtoOxy)
Other intervention
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.
Unilateral hypoglossal nerve stimulation (HGNS), active comparator condition
Device
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.
Atomoxetine-plus-oxybutynin (80/5 mg) (AtoOxy), active comparator condition
Drug
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
Placebo; placebo comparator condition
Drug
Matching placebo capsules administered orally at bedtime. HGNS device off

Treatment groups

24 Participants

are divided into 4 treatment groups

Group A: Sequence 1Other 4 interventions

Group B: Sequence 2Other 4 interventions

Group C: Sequence 3Other 4 interventions

Group D: Sequence 4Other 4 interventions

Trial outcomes

Primary outcomes

Apnea-Hypopnea Index

Apnea-hypopnea index (AHI), defined as the number of apneas and hypopneas per hour of sleep, measured by overnight polysomnography at the end of each treatment period. Quantitative outcome variable: percent change (symmetrized) from baseline.

Time frame

2 Weeks

Secondary outcomes

Hypoxic Burden

Hypoxic burden, defined as the area under the oxygen desaturation curve associated with respiratory events multiplied by event frequency, measured during overnight polysomnography. Quantitative outcome variable: percent change (symmetrized) from baseline.

Time frame

2 Weeks

Visual Analog Scale for Sleep Quality

Self-reported sleep quality measured using a visual analog scale. Quantitative outcome variable: absolute change from baseline. Range: 0-10 (higher values indicate greater sleep quality).

Time frame

2 Weeks

Other outcomes

Epworth Sleepiness Scale (ESS)

Daytime sleepiness assessed using the Epworth Sleepiness Scale (range 0-24, higher scores indicate greater sleepiness). Quantitative outcome variable: absolute change from baseline.

Time frame

2 Weeks

Visual Analog Scale for Treatment Satisfaction

Self-reported treatment satisfaction measured using a visual analog scale. Quantitative outcome variable: absolute value on treatment. Range: 0-10 (higher values indicate greater treatment satisfaction).

Time frame

2 Weeks

Sleep Apnea Quality of Life Index (SAQLI)

Disease-specific quality of life assessed using the Sleep Apnea Quality of Life Index. Quantitative outcome variable: absolute change from baseline. Range: 1-7 (higher values indicate greater sleep apnea-related quality of life).

Time frame

2 Weeks

PROMIS Sleep-Related Impairment

Patient-reported outcomes assessing sleep-related impairment: Quantitative outcome variable: absolute change from baseline. Range: 0-100 (mean 50, SD 10; higher T-scores indicate greater impairment).

Time frame

2 Weeks

Sponsors and contacts

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Brigham and Women's Hospital

Lead sponsor

Source ClinicalTrials.gov

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