Obstructive Sleep Apnea, Sleep Disordered Breathing
Conditions
Keywords
Obstructive sleep apnea, Hypoglossal nerve stimulation, Tonsillectomy
Brief summary
The goal of this clinical trial is to learn whether removing the tonsils at the time of hypoglossal nerve stimulation improves treatment of obstructive sleep apnea in adults whose airway collapses from the side of the upper airway during sleep. The main questions it aims to answer are: 1. Does hypoglossal nerve stimulation combined with tonsillectomy reduce the severity of obstructive sleep apnea more than hypoglossal nerve stimulation alone? 2. Does tonsillectomy improve how effectively hypoglossal nerve stimulation opens and stabilizes the upper airway? Researchers will compare participants who receive hypoglossal nerve stimulation with tonsillectomy to participants who receive hypoglossal nerve stimulation alone. Participants will: * Complete sleep studies, questionnaires, and other assessments before and after treatment * Be randomly assigned to receive hypoglossal nerve stimulation either with or without tonsillectomy * Return for follow-up visits and sleep testing to evaluate treatment effectiveness * In a subset of participants, complete additional overnight testing to measure how treatment changes upper-airway collapsibility
Detailed description
Obstructive sleep apnea (OSA) is commonly treated with hypoglossal nerve stimulation (HGNS), but treatment efficacy is substantially reduced in patients with complete oropharyngeal lateral wall (OPLW) collapse. HGNS primarily enlarges the airway by protruding the tongue and is therefore most effective in patients with anteroposterior patterns of airway collapse. Tonsillectomy reduces tissue contributing to lateral pharyngeal narrowing and may complement the mechanism of HGNS by addressing residual lateral wall obstruction. Preliminary clinical data suggest that combining tonsillectomy with HGNS substantially improves treatment response compared with HGNS alone in patients with OPLW collapse, but this strategy has not been evaluated in a randomized clinical trial. This prospective, randomized controlled trial will enroll 72 adults with moderate-to-severe OSA, complete OPLW collapse identified on drug-induced sleep endoscopy, and candidacy for both HGNS implantation and tonsillectomy. Participants will be randomized 1:1 to receive either concurrent HGNS implantation plus tonsillectomy or HGNS implantation alone. All participants will undergo standard postoperative device activation and titration. The primary efficacy endpoint will be assessed after approximately one month of optimized HGNS therapy using sleep studies and patient-reported outcomes. Participants in the HGNS-alone group with persistent OSA may subsequently undergo delayed tonsillectomy as part of standard clinical care, permitting additional within-subject mechanistic comparisons. The primary objective is to determine whether concurrent tonsillectomy improves the effectiveness of HGNS in reducing OSA severity compared with HGNS alone. Secondary objectives are to determine whether tonsillectomy enhances HGNS-induced improvements in upper-airway collapsibility and to evaluate whether tonsillectomy modifies the physiological effects of HGNS beyond the effects of either treatment alone. In an optional mechanistic substudy, approximately 30 participants will undergo detailed physiological sleep studies to measure pharyngeal collapsibility using gold-standard techniques, providing insight into the mechanisms underlying any observed improvement in clinical outcomes.
Interventions
PROCEDURETonsillectomy
Tonsillectomy
DEVICEHGNS
HGNS alone (without concomitant tonsillectomy)
Sponsors
Brigham and Women's Hospital
Massachusetts Eye and Ear Infirmary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Because treatment assignment determines the surgical procedure and subsequent study schedule, participants, treating surgeons, and study personnel responsible for clinical care, safety monitoring, scheduling, and study operations will not be blinded to treatment assignment. Outcomes assessors (e.g., principal investigator, postdoc fellow) may become aware of treatment assignment through protocol oversight or participant safety monitoring but will not participate in blinded primary outcome scoring. To minimize assessment bias, sleep studies used for the primary endpoint will be prepared by an unblinded study team member not involved in outcome assessment. Files will be assigned blinded assessment identifiers and stripped of treatment assignment and other information that could reveal allocation. Primary endpoint scoring will be performed by personnel blinded to treatment assignment, and the primary analysis will be conducted using coded treatment groups until the analysis is finalized.
Intervention model description
This study is a prospective, parallel-group, randomized controlled trial evaluating whether concurrent tonsillectomy enhances the effectiveness of hypoglossal nerve stimulation (HGNS) in adults with obstructive sleep apnea and complete oropharyngeal lateral wall collapse. Participants will be randomized in a 1:1 ratio to receive either HGNS implantation with concurrent tonsillectomy (HGNS+T) or HGNS implantation alone. The primary analysis will compare clinical outcomes between the two randomized groups after approximately one month of optimized HGNS therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosis of obstructive sleep apnea with apnea-hypopnea index (AHI) ≥ 15 events/hour * Complete oropharyngeal lateral wall (OPLW) collapse identified on DISE * Candidate for HGNS implantation based on standard clinical criteria * Presence of small (1-2+) tonsils and eligibility for tonsillectomy * Untreated OSA at the time of enrollment * Willing and able to provide written informed consent
Exclusion criteria
* Absence of tonsils * Presence of large tonsils (3-4+; not eligible for HGNS) * Predominant central or mixed sleep apnea (\>25% central or mixed events) * Any unstable or serious medical condition that, in the opinion of the investigator, would increase risk or interfere with study participation * Ineligibility for HGNS implantation based on standard clinical or surgical criteria * Inability to comply with study procedures or follow-up assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent reduction in apnea-hypopnea index (AHI) | 1 month of optimized therapy. | Percent reduction in the apnea-hypopnea index (AHI), measured by overnight polysomnography, from baseline to the primary follow-up sleep study. Higher values indicate greater improvement in obstructive sleep apnea. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change in apnea-hypopnea index | 1 month of optimized therapy. | Absolute change in the apnea-hypopnea index (AHI), measured in events per hour by overnight polysomnography, from baseline to the primary follow-up sleep study. Negative values indicate improvement in obstructive sleep apnea. |
| Treatment success | 1 month of optimized therapy | Treatment success is defined as a ≥50% reduction in the apnea-hypopnea index (AHI) from baseline and a follow-up AHI \<15 events per hour. The outcome is reported as the proportion of participants meeting this definition (0-100%), with higher values indicating greater treatment success. |
| Change in Sleep Apnea Hypoxic Burden from Baseline | 1 month of optimized therapy | Sleep apnea hypoxic burden will be calculated from overnight polysomnography using the validated Azarbarzin method (PMID: 30376054) as the cumulative area under the oxygen desaturation curve associated with apneas and hypopneas, normalized to total sleep time and expressed as %min/hour. Higher values indicate greater hypoxic burden. |
Countries
United States
Contacts
CONTACTDaniel Vena, PhD
CONTACTDillon Gilbertson, BASc
Outcome results
None listed