Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

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

4 maggio 2026 aggiornato da: Scott Aaron Sands, Brigham and Women's Hospital

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

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

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.

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

24

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria 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).

Exclusion Criteria:

  • 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:

      1. "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?"
      2. "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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Altro: Sequence 1

HGNS+AtoOxy -> Placebo -> HGNS -> AtoOxy

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.
Altro: 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.

Altri nomi:
  • HGNS+AtoOxy
Dispositivo: 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.

Altri nomi:
  • HGNS
Droga: 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

Altri nomi:
  • AtoOxy
Droga: Placebo; placebo comparator condition
Matching placebo capsules administered orally at bedtime. HGNS device off
Altri nomi:
  • Placebo
Altro: Sequence 2

HGNS -> AtoOxy -> HGNS+AtoOxy -> Placebo

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.
Altro: 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.

Altri nomi:
  • HGNS+AtoOxy
Dispositivo: 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.

Altri nomi:
  • HGNS
Droga: 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

Altri nomi:
  • AtoOxy
Droga: Placebo; placebo comparator condition
Matching placebo capsules administered orally at bedtime. HGNS device off
Altri nomi:
  • Placebo
Altro: Sequence 3

AtoOxy -> HGNS -> Placebo -> HGNS+AtoOxy

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.
Altro: 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.

Altri nomi:
  • HGNS+AtoOxy
Dispositivo: 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.

Altri nomi:
  • HGNS
Droga: 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

Altri nomi:
  • AtoOxy
Droga: Placebo; placebo comparator condition
Matching placebo capsules administered orally at bedtime. HGNS device off
Altri nomi:
  • Placebo
Altro: Sequence 4

Placebo -> HGNS+AtoOxy -> AtoOxy -> HGNS

Each participant receives all four treatment conditions ("periods") in randomized order; outcomes are analyzed as within-subject comparisons, not between sequence arms.
Altro: 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.

Altri nomi:
  • HGNS+AtoOxy
Dispositivo: 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.

Altri nomi:
  • HGNS
Droga: 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

Altri nomi:
  • AtoOxy
Droga: Placebo; placebo comparator condition
Matching placebo capsules administered orally at bedtime. HGNS device off
Altri nomi:
  • Placebo

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Apnea-Hypopnea Index
Lasso di tempo: 2 Weeks

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.
2 Weeks

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Hypoxic Burden
Lasso di tempo: 2 Weeks

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.
2 Weeks
Visual Analog Scale for Sleep Quality
Lasso di tempo: 2 Weeks
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).
2 Weeks

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Epworth Sleepiness Scale (ESS)
Lasso di tempo: 2 Weeks

Daytime sleepiness assessed using the Epworth Sleepiness Scale (range 0-24, higher scores indicate greater sleepiness).

Quantitative outcome variable: absolute change from baseline.
2 Weeks
Visual Analog Scale for Treatment Satisfaction
Lasso di tempo: 2 Weeks
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).
2 Weeks
Sleep Apnea Quality of Life Index (SAQLI)
Lasso di tempo: 2 Weeks

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).
2 Weeks
PROMIS Sleep-Related Impairment
Lasso di tempo: 2 Weeks

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).
2 Weeks
PROMIS Fatigue
Lasso di tempo: 2 Weeks

Patient-reported outcomes assessing fatigue: Quantitative outcome variable: absolute change from baseline.

Range: 0-100 (mean 50, SD 10; higher T-scores indicate greater fatigue).
2 Weeks
PROMIS Sleep Disturbance
Lasso di tempo: 2 Weeks

Patient-reported outcomes assessing sleep disturbance: Quantitative outcome variable: absolute change from baseline.

Range: 0-100 (mean 50, SD 10; higher T-scores indicate greater sleep disturbance).
2 Weeks

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Brigham and Women's Hospital

Investigatori

  • Investigatore principale: Scott A Sands, PhD, Brigham and Women's Hospital

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 giugno 2026

Completamento primario (Stimato)

1 dicembre 2027

Completamento dello studio (Stimato)

1 dicembre 2027

Date di iscrizione allo studio

Primo inviato

27 aprile 2026

Primo inviato che soddisfa i criteri di controllo qualità

4 maggio 2026

Primo Inserito (Effettivo)

11 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

11 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

4 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2026P000970

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

INDECISO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

Sì

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Apnea ostruttiva del sonno

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Germany

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi