Combination Tonsillectomy and Hypoglossal Nerve Stimulation for OSA Patients With Lateral Pharyngeal Collapse (HGNS+T)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Obstructive Sleep Apnea; Sleep Disordered Breathing
• Intervention / Treatment: Procedure: Tonsillectomy; Device: HGNS

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.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dillon Gilbertson, BASc; Phone Number: 617-732-6488; Email: dgilbertson@bwh.harvard.edu
• Study Contact Backup: Name: Daniel Vena, PhD; Phone Number: 16178520719; Email: dvena@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HGNS plus tonsillectomy; HGNS plus concomitant tonsillectomy	Procedure: Tonsillectomy; Tonsillectomy; Device: HGNS; HGNS alone (without concomitant tonsillectomy)
Active Comparator: HGNS; HGNS alone (without concomitant tonsillectomy)	Device: HGNS; HGNS alone (without concomitant tonsillectomy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent reduction in apnea-hypopnea index (AHI)	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.	1 month of optimized therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in apnea-hypopnea index	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.	1 month of optimized therapy.
Treatment success	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.	1 month of optimized therapy
Change in Sleep Apnea Hypoxic Burden from Baseline	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.	1 month of optimized therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Sleep Disturbance	The PROMIS Sleep Disturbance Short Form 8b assesses perceptions of sleep quality, sleep depth, and difficulties with sleep. Scores are reported as standardized T-scores (mean = 50 and SD = 10), with higher scores indicating greater sleep disturbance (worse outcome).	1 month of optimized therapy
PROMIS Sleep-Related Impairment	The PROMIS Sleep-Related Impairment Short Form 8a assesses daytime impairment associated with poor sleep, including sleepiness, fatigue, and reduced alertness. Scores are reported as standardized T-scores (mean = 50 and SD = 10), with higher scores indicating greater sleep-related impairment (worse outcome).	1 month of optimized therapy
PROMIS Fatigue	The PROMIS Fatigue Short Form 7a assesses the experience and impact of fatigue on daily functioning. Scores are reported as standardized T-scores (mean = 50 and SD = 10), with higher scores indicating greater fatigue (worse outcome).	1 month of optimized therapy
Sleep apnea quality of life	The Sleep Apnea Quality of Life Index (SAQLI) assesses disease-specific quality of life in obstructive sleep apnea. Total scores range from 1 to 7, with higher scores indicating better sleep-related quality of life (better outcome).	1 month of optimized therapy
Epworth sleepiness scale	The Epworth Sleepiness Scale assesses subjective daytime sleepiness. Total scores range from 0 to 24, with higher scores indicating greater daytime sleepiness (worse outcome).	1 month of optimized therapy
VAS treatment satisfaction	Participants rate overall satisfaction with treatment on a 0-10 visual analog scale, where 0 indicates not at all satisfied and 10 indicates completely satisfied. Higher scores indicate greater treatment satisfaction (better outcome).	1 month of optimized therapy

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Massachusetts Eye and Ear Infirmary

Publications and helpful links

General Publications

• Huyett P, Kent DT, D'Agostino MA, Green KK, Soose RJ, Kaffenberger TM, Woodson BT, Huntley C, Boon MS, Heiser C, Birk A, Suurna MV, Lin HS, Waxman JA, Kezirian EJ. Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study. Laryngoscope. 2021 Jul;131(7):1676-1682. doi: 10.1002/lary.29396. Epub 2021 Jan 14.
• Vena D, Op de Beeck S, Yang H, Sumner J, Mann D, Wang TY, Aishah A, Azarbarzin A, Messineo L, Calianese N, Alex R, Esmaeili N, Vanderveken OM, White DP, Wellman A, Huyett P, Sands SA. Lateral wall collapse from sleep endoscopy and airflow shape predicts hypoglossal nerve stimulation efficacy in obstructive sleep apnoea. Eur Respir J. 2025 Oct 7;66(4):2500236. doi: 10.1183/13993003.00236-2025. Print 2025 Oct.
• Huyett P, Wellman A, Caruso V, Sumner J, Aishah A, Azarbarzin A, Sands S, Vena D. Combination Tonsillectomy and Hypoglossal Nerve Stimulation for Sleep Apnea Patients With Oropharyngeal Lateral Wall Collapse. Otolaryngol Head Neck Surg. 2024 Dec;171(6):1904-1910. doi: 10.1002/ohn.950. Epub 2024 Aug 27.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Obstructive sleep apnea; Hypoglossal nerve stimulation; Tonsillectomy
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Otorhinolaryngologic Surgical Procedures; Tonsillectomy
• Other Study ID Numbers: 2026P000343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No