Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS)

NCT05508971 | Recruiting DMC

• 2 other identifiers: STUDY000247461R61HL165345
• Study Type: interventional
• Target: 303
• Locations: 1 country
• Sites: 7

Brief Summary

The overall objective of this randomized clinical trial is to test the effectiveness of a personalized approach to the surgical treatment of OSA in children with Down syndrome (DS).The estimated prevalence of obstructive sleep apnea (OSA) in children with DS ranges from 45-83%, compared to 1-6% in the general pediatric population. Untreated OSA in children has been associated with daytime sleepiness, cognitive or behavioral problems, and cardiovascular complications, all which are common in children with DS. Adenotonsillectomy (AT) is the first line treatment for OSA in children, however, most large studies of AT outcomes have excluded children with DS. Available evidence demonstrates that AT is far less effective in children with DS than in the general pediatric population, with 48 to 95% of children with DS having persistent OSA after AT. Medical treatments such as positive airway pressure (PAP) therapy are frequently inadequate or poorly tolerated in this population, so many children with DS and OSA remain untreated. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of obstruction during sedated sleep using a flexible endoscope passed through the nose into the pharynx. 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. Using this DISE Rating Scale, the investigators have demonstrated that children with DS are more prone to tongue base and supraglottic obstruction than non-DS children, suggesting the need for more personalized surgical treatments that are tailored to the common sources of obstruction in this population. Several small case series demonstrate that DISE-directed surgery can be effective in treating OSA in children with DS. However, because there have been few prospective studies and no randomized trials comparing different treatment options in this population, there remains uncertainty about whether such a personalized approach leads to superior outcomes compared to the first line AT. It is the investigators' hypothesis that personalized DISE-directed surgery that uses existing procedures to address specific fixed and dynamic anatomic features causing obstruction in each child with DS will be superior to the current 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.

Conditions

Obstructive Sleep Apnea; Down Syndrome

Outcome Measures

Primary Outcomes (7)

• Change from Baseline Polysomnography Measures: 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

  6 month follow up sleep study (after surgery)

• Change from Baseline Polysomnography Measures: 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

  6 month follow up sleep study (after surgery)

• Change from Baseline Polysomnography Measures: 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

  6 month follow up sleep study (after surgery)

• Change from Baseline Polysomnography Measures: min 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

  6 month follow up sleep study (after surgery)

• Change from Baseline Polysomnography Measures: desat index at 6 months

  Oxyhemoglobin desaturation ≥ 3% Index: 6 months follow up sleep study difference from baseline sleep study

  6 month follow up sleep study (after surgery)

• Change from Baseline Polysomnography Measures: % 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

  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

  6 month follow up sleep study (after surgery)

Secondary Outcomes (6)

• Change in Obstructive Sleep Apnea (OSA)-18 Questionnaire score

  6 month follow up

• Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire score

  6 month follow up

• Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire answers

  6 month follow up

• Total Drug induced sleep endoscopy (DISE) score

  At time of surgery

• Adverse Events

  24 hour period after surgery

Study Arms (2)

Drug-Induced Sleep Endoscopy

EXPERIMENTAL

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

Adenotonsillectomy

ACTIVE COMPARATOR

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

Interventions

DISE-Directed Surgery PROCEDURE

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.

Drug-Induced Sleep Endoscopy

Adenotonsillectomy PROCEDURE

Tonsil and adenoid removal

Also known as: AT

Adenotonsillectomy

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

Requirements to participate in study: Child has a diagnosis of Down syndrome (Trisomy 21). 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. 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 participate in 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. Caregiver is unwilling or unable to comply with study procedures. Child is or plans to have their own child.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of Michigan: collaborator
• University of Texas: collaborator
• Eastern Virginia Medical School: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Texas Children's: collaborator
• Children's Hospital Colorado: collaborator

Study Sites (7)

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

ACTIVE NOT RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

NOT YET RECRUITING

EVMS Medical School

Norfolk, Virginia, 23507, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Down Syndrome

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Derek Lam, MD, MPH

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eleni O'Neill

CONTACT

503-875-9895; topsds@ohsu.edu

Derek Lam, MD

CONTACT

503-494-9419; lamde@ohsu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: It is not practical or feasible to maintain blinding among the surgeons performing the procedures or the clinical staff caring for patients in the perioperative setting. Given this, it is unlikely that blinding could be maintained among parents or caregivers of patients, therefore there will be no attempt to blind caregivers to the treatment assignment. However, the sleep medicine collaborators who will be reviewing and scoring postoperative PSGs will be instructed not to review the medical record so as to ensure blinding to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Otolaryngology - Head and Neck Surgery

Model Details: Participants will be recruited from pediatric otolaryngology clinics. The study will be introduced to caregivers of children with DS and a history of sleep disordered breathing/OSA who are referred for surgery and meet the study participation criteria noted. If current or recent PSG testing demonstrates OSA, they will be invited to participate. Randomization will be done. Patients will be randomized to either the personalized DISE-directed surgery or the standard AT after collection of baseline measures and pre-op PSG. Allocation will be made by using a computer-generated randomization scheme. Caregivers will be advised of the outcomes and risks of different surgical procedures included in DISE-directed surgery and informed consent will be obtained. All patients will be planned for overnight observation to monitor for safety and periop complications.

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 19, 2022
• Study Start: August 2, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)