Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Small Tonsils

Obstructive Sleep Apnea Clinical Trial

— TOPS-ST  

Official title:

Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Small Tonsils

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06258837
• Other study ID #: STUDY00027270
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: September 30, 2028

Study information

• Verified date: May 2024
• Source: Oregon Health and Science University
• Contact: Eleni O'Neill
• Phone: 503-494-3569
• Email: oneilele[@]ohsu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: September 30, 2028
• Est. primary completion date: June 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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 pregnant.

• Child is eligible for surgical treatment

Exclusion Criteria:

• 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 pregnant.

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Otolaryngological Disease
• Otorhinolaryngologic Diseases
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

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.
• Adenotonsillectomy
Tonsil and/or adenoid removal

Locations

Country	Name	City	State
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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