Combination Upper-Airway Electrical and Pharmacological Stimulation for Obstructive Sleep Apnea: A Randomized-Controlled Trial.

Brigham and Women's Hospital2 个研究点分布在 1 个国家目标入组 24 人开始时间: 2026年6月1日最近更新: 2026年5月11日

干预措施

试验速览

阶段: 1 期
状态: 尚未招募
发起方: Brigham and Women's Hospital
入组人数: 24
试验地点: 2

研究概览研究设计入排标准研究组 & 干预措施研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

Residual obstructive sleep apnea (OSA) is common among patients treated with hypoglossal nerve stimulation (HGNS), reflecting incomplete correction of underlying pathophysiological traits. In addition to upper airway collapsibility, non-anatomical factors such as a low arousal threshold may contribute to persistent disease despite HGNS therapy. Pharmacologic modulation of these traits represents a potential strategy to enhance treatment efficacy.

Atomoxetine (a norepinephrine re-uptake inhibitor) and oxybutynin (an anti-muscarinic agent) have been shown to increase upper airway muscle tone and raise the arousal threshold, leading to reductions in OSA severity in prior studies. However, their combined effect when added to ongoing HGNS therapy has not been systematically evaluated.

This study is a randomized, placebo-controlled, crossover trial designed to assess the acute effects of combined pharmacologic and electrical stimulation on OSA severity. Participants with OSA who are already implanted with HGNS, or pending clinical implantation, will be enrolled in a four-period randomized placebo-controlled cross-over trial assessing HGNS+AtoOxy, HGNS alone (plus placebo), AtoOxy alone (HGNS device off), and placebo (HGNS device off).

Polysomnographic measurements will be also be used to explore mechanisms underlying response, including the interaction between pharmacologically modifiable traits and HGNS-mediated airway stabilization. Additional analyses will evaluate whether baseline physiological characteristics predict treatment response, with the goal of informing personalized treatment strategies for patients with residual OSA. Patient-reported outcomes, including sleepiness, sleep-related quality of life, fatigue, and treatment satisfaction, will also be assessed to evaluate the broader clinical impact of the combination intervention.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Treatment
盲法: Triple (Participant, Investigator, Outcomes Assessor)

盲法说明

Medication (atomoxetine plus oxybutynin vs placebo) is double-blinded to participants, investigators, and outcomes assessors. Hypoglossal nerve stimulation (HGNS) cannot be blinded, as device activation status must be known to study staff and participants. Randomization procedures are designed to maintain blinding of medication assignment while allowing appropriate administration of HGNS.

入排标准

年龄范围: 18 Years 至 79 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•for Enrolment:
•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).

排除标准

•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)
•Excluded: History of traffic accidents attributable to sleepiness or fatigue (<2 years).
•Use of SNRIs/SSRIs or anticholinergic medications during the study.
•Conditions likely to affect obstructive sleep apnea physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
•Respiratory disorders other than sleep disordered breathing:
•chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
•Other sleep disorders: narcolepsy, parasomnias. Insomnia
•Contraindications for atomoxetine and oxybutynin, including:
•hypersensitivity to atomoxetine or oxybutynin (angioedema or urticaria)
•pheochromocytoma
•use of monoamine oxidase inhibitors
•diagnosed benign prostatic hypertrophy, urinary retention
•suspected benign prostatic hypertrophy / urinary retention based on a positive answer to either of the following questions:
•"During the last month, when urinating, have you had the sensation of not emptying your bladder completely more often than 1 out of 5 times?"
•"During the last month, have you had a weak urinary stream more often than 1 out of 5 times?
•known untreated narrow angle glaucoma
•known bipolar disorder, mania, psychosis
•known history of major depressive disorder (age<24).
•known history of attempted suicide or suicidal ideation within one year prior to screening
•known clinically significant constipation, gastric retention
•known pre-existing seizure disorders
•known clinically-significant kidney disorders (eGFR<60 ml/min/1.73m2)
•known clinically-significant liver disorders
•known clinically-significant cardiovascular conditions
•moderate-to-severe hypertension (SBP>160 mmHg or DBP>100 mmHg measured at baseline; average of evening and morning measures)
•known cardiomyopathy (LVEF<50%) or heart failure
•known advanced atherosclerosis
•recent cerebrovascular events (within 2 years)
•recent history of cardiac arrhythmias e.g., atrial fibrillation, QT prolongation (within 2 years)
•other serious cardiac conditions that would raise the consequences of an increase in blood pressure or heart rate
•myasthenia gravis
•pregnancy/breast-feeding