Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Small Tonsils (TOPS-ST)

The purpose of this study is to compare the effectiveness of a novel personalized surgical approach to the standard AT in children with small tonsils (ST). This will be accomplished by randomizing children with ST and OSA to one of these two treatments and comparing outcomes after 6 months. It is the investigators' central hypothesis that a personalized drug-induced sleep endoscopy (DISE)-directed surgical approach that uses existing procedures to address the specific fixed and dynamic anatomic features causing obstruction (ie, anatomic endotypes) in each child with ST will perform better than the currently recommended standard first line approach of AT. This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT. To test this hypothesis, the investigators propose to study children aged 2-17 years with small tonsils and OSA.

Study Overview

• Status: Recruiting
• Conditions: Obstructive Sleep Apnea; Otolaryngological Disease
• Intervention / Treatment: Procedure: DISE-Directed Surgery; Procedure: Adenotonsillectomy

Detailed Description

Obstructive sleep apnea (OSA) is common in children with an estimated prevalence of 1-6%. Untreated pediatric OSA is associated with hypertension, autonomic dysfunction, attention-deficit / hyperactivity disorder, neurocognitive deficits, poor school performance, poor quality of life, and a >200% increase in health care utilization compared to controls. Adenotonsillar hypertrophy is the primary risk factor for pediatric OSA, and adenotonsillectomy (AT) is the recommended first line treatment. However, the prevalence of persistent OSA after AT has been reported to be at least 20% among children with large tonsils, indicating that AT may not be the optimal intervention in all cases. Although the prevalence of small tonsils in children with OSA symptoms is up to 70%, there is currently no clear evidence on the outcome of AT in children with small tonsils. It has been shown that clinic assessments of tonsil size do not correlate with OSA severity or response to AT, leaving confusion about how best to treat OSA in children with small tonsils. This knowledge gap represents an opportunity to apply a personalized treatment approach and improve outcomes.

DISE entails passage of a flexible endoscope through the nose into the pharynx and enables direct observation of the sites and patterns of upper airway obstruction during sedated sleep. DISE was developed to guide surgical decisions in adult OSA, and in recent years has also been used to design personalized surgical interventions in children. To help standardize DISE assessments, the investigators previously developed and validated the DISE Rating Scale in children based on ordinal ratings of maximal airway obstruction (none, partial, complete) at six anatomic sites from the nose to the larynx.

The investigators also demonstrated that DISE ratings of adenotonsillar obstruction during sedated sleep are strongly associated with both OSA severity and response to AT, unlike clinic assessments of tonsil size. The investigators' preliminary data and other published studies have identified a high prevalence of non-adenotonsillar obstruction that can occur at the nose, palate, base of tongue, and larynx. Surgery that is tailored to the specific anatomic sites of obstruction observed during DISE may improve pediatric OSA outcomes, but existing studies are small, uncontrolled case series in heterogeneous study populations. There are no trials directly comparing AT and DISE-directed surgery in the common scenario of surgically naïve children with small tonsils.

The purpose of this study is to compare the effectiveness of a novel personalized surgical approach to the standard AT in children with small tonsils (ST). This will be accomplished by randomizing children with ST and OSA to one of these two treatments and comparing outcomes after 6 months. It is the investigators' central hypothesis that a personalized drug-induced sleep endoscopy (DISE)-directed surgical approach that uses existing procedures to address the specific fixed and dynamic anatomic features causing obstruction (i.e., anatomic endotypes) in each child with ST will perform better than the currently recommended standard first line approach of AT. This novel approach may improve OSA outcomes and reduce the burden of unnecessary AT or secondary surgery for persistent OSA after an ineffective AT. To test this hypothesis, the investigators propose to study children aged 2-17 years with small tonsils and OSA.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Derek Lam, MD; Phone Number: 503-494-9419; Email: lamde@ohsu.edu
• Study Contact Backup: Name: Eleni O'Neill; Phone Number: 503-494-3569; Email: oneilele@ohsu.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Brittany Nordhaus; Email: nbrittan@med.umich.edu
      • Principal Investigator: Erin Kirkham, MD, MPH
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Principal Investigator: Derek Lam, MD, MPH
      • Contact: Eleni O'Neill; Phone Number: 503-875-9895; Email: topsst@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

To be in the study:

• Child has a diagnosis of moderate to severe OSA diagnosed by PSG (oAHI ≥ 5).
• Child age is 2.00 to 17.99 years of age.
• Child has small tonsils (Brodsky 1+ or 2+) noted during routine physical exam.
• Caregiver can provide signed and dated consent and is 18 years of age or older at the time of consent.
• Caregiver can speak, read, and write in English or Spanish.
• Caregiver is primary caretaker of the child.
• Child is not expecting their own child.
• Child is eligible for surgical treatment

Cannot be in the study if:

• Child has history of previous tonsillectomy, tonsillotomy, or partial tonsillectomy.
• Child has any contraindication to surgery (e.g. bleeding disorders).
• Child has significant cardiopulmonary comorbidity besides OSA requiring supplemental oxygen, subglottic or tracheal stenosis, tracheostomy dependence.
• Child has a genetic abnormality, Down syndrome, neuromuscular disorder, craniofacial anomaly.
• Caregiver is unwilling or unable to comply with study procedures.
• Child is or plans to become a parent themselves.

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: Drug-Induced Sleep Endoscopy; DISE will be performed at the time of surgery under the same sedation. The decision on specific surgical approach will be made at that time based on DISE findings. Prior to intubation, patients will be sedated with either a propofol infusion or a combination of ketamine and dexmedetomidine. Once adequate sedation is achieved, endoscopy will be performed using a flexible endoscope advanced through the nose. The nasal airway will be evaluated on both sides, then the endoscope will be advanced into the pharynx. The degree of obstruction is scored on a 3-point rating scale. Participants randomized to DISE-directed surgery will undergo one or more potential procedures in a single surgery. Caregivers will be consented for all possible procedures with the understanding that only those needed based on DISE will be performed. Importantly, these procedures are all established treatments with published outcomes data.	Procedure: DISE-Directed Surgery; Participants randomized to DISE-directed surgery will undergo one or more potential procedures in a single surgery (i.e. DISE and subsequent sleep surgery performed) concurrently under the same general anesthetic), depending on anatomic assessment.; Other Names: sleep endoscopy
Active Comparator: Adenotonsillectomy; Adenotonsillar hypertrophy is the most common risk factor for OSA in children, and adenotonsillectomy (AT) is the first line treatment. An adenotonsillectomy is an operation to remove both the adenoids and tonsils.	Procedure: Adenotonsillectomy; Tonsil and/or adenoid removal; Other Names: AT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Polysomnography Measures: Obstructive Apnea-Hypopnea Index (oAHI) at 6 months	Objective results from sleep studies (polysomnography): Obstructive Apnea-Hypopnea Index (oAHI): 6 months follow up sleep study difference from baseline sleep study. Higher scores indicate higher disease burden. Scores can range from zero to two hundred.	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: Total Apnea-Hypopnea Index (AHI) at 6 months	Objective results from sleep studies (polysomnography): Total Apnea-Hypopnea Index: 6 months follow up sleep study difference from baseline sleep study. Higher scores indicate higher disease burden. Scores can range from zero to two hundred.	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: REM Apnea-Hypopnea Index (REM AHI) at 6 months	Objective results from sleep studies (polysomnography): REM Apnea-Hypopnea Index REM AHI: 6 months follow up sleep study difference from baseline sleep study. Higher scores indicate higher disease burden. Scores can range from zero to two hundred.	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: minimum Oxygen saturation (SpO2) at 6 months	Objective results from sleep studies (polysomnography): Minimum Oxygen Saturation (Min SpO2): 6 months follow up sleep study difference from baseline sleep study. Lower scores indicate higher disease burden. Scores range from 0-100, although neither extreme is actually seen in patients.	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: Oxyhemoglobin desaturation ≥ 3% Index (desat index) at 6 months	Oxyhemoglobin desaturation ≥ 3% Index: 6 months follow up sleep study difference from baseline sleep study. Higher scores mean higher disease burden. Mild desaturation (< 5.0 events/h), moderate desaturation (≥ 5.0 events/h and < 10.0 events/h), and severe desaturation (≥ 10.0 events/h).	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: Percent Total Sleep Time with ETCO2 > 50 mmHg at 6 months	% Total Sleep Time with ETCO2 > 50 mmHg: 6 months follow up sleep study difference from baseline sleep study. Higher scores mean higher disease burden. Scores range from 0-100.	6 month follow up sleep study (after surgery)
Change from Baseline Polysomnography Measures: Max End Tidal CO2 (ETCO2) at 6 months	Max End Tidal CO2 (ETCO2): 6 months follow up sleep study difference from baseline sleep study. Higher scores mean higher disease burden. Normal is 35-40 mmHg.	6 month follow up sleep study (after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Obstructive Sleep Apnea (OSA)-18 Questionnaire score	Disease specific quality of life measure: 18 questions, scores range from 18-126; higher scores means higher disease burden	6 month follow up
Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire score	Generic quality of life measure: an age specific questionnaire with 23 questions (scores range from 0-100); higher scores indicate better quality of life.	6 month follow up
Total Drug induced sleep endoscopy (DISE) score	Subjective ratings of degree of obstruction at 6 levels of the upper airway, done by surgeon. Scores range from 0 to 12. Higher scores means more breathing obstruction, or more disease burden.	At time of surgery
Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire answers	Quality of life: questionnaire results by individual question. Adjusted scores range from 0-100; higher scores indicate better quality of life.	6 month follow up
Adverse Events	Did any adverse events occur in the post-operative time frame? This is a yes/no question, looking at the following outcomes: dehydration and poor oral intake due to post-operative pain, post-tonsillectomy hemorrhage, and respiratory compromise.	24 hour period after surgery
Change in Child Behavior Checklist (CBCL) Questionnaire answers	Assesses behavioral and emotional problems: questionnaire results by total score and by "syndrome scale scores". Adjusted norms scores range from 0.0-1.0; higher scores indicate greater problems.	Baseline versus 6 month follow up

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: University of Michigan
• Investigators: Principal Investigator: Derek Lam, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• 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; Otorhinolaryngologic Diseases
• Other Study ID Numbers: STUDY00027270

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be made available to researchers who are not primary researchers on this study.

Drug and device information, study documents

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