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

NCT ID: NCT05508971

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 303 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-02
• Study Completion Date: 2027-06-30

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.

Detailed Description

The overall objective of this randomized clinical trial is to test the effectiveness of a novel personalized approach to the surgical treatment of OSA in children with Down syndrome (DS). DS is a common disorder, affecting 1 in 691 births. 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 and behavioral problems, and cardiovascular complications, all of 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.

Pharyngeal hypotonia, unfavorable craniofacial anatomy, and adiposity are commonly cited risk factors for OSA and failure of AT in children with DS, however, there have been few attempts to characterize the pharyngeal anatomy or mechanisms of obstruction in this population. Drug-induced sleep endoscopy (DISE) enables direct observation of the sites and patterns of pharyngeal 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. 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. 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' central hypothesis that a personalized DISE-directed surgical approach that uses existing procedures to address the specific fixed and dynamic anatomic features causing obstruction in each child with DS will be superior to the currently recommended 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 with DS and OSA ages 2-17 years with the following specific aims:

Aim 1: Compare the physiological outcomes of DISE-directed surgery vs AT in children with DS and OSA.

Hypothesis 1: DISE-directed surgery will result in a greater improvement in the obstructive apnea-hypopnea index compared to the standard AT intervention (effect size ≥ 0.36) after 6 months.

Aim 2: Compare the clinical outcomes of DISE-directed surgery vs AT in children with DS and OSA.

Hypothesis 2: DISE-directed surgery will result in a clinically significantly greater improvement (≥ 9 point improvement) in OSA-specific quality of life (OSA-18) compared to the standard AT intervention after 6 months. Secondarily, the investigators will test other clinical outcomes such as executive function (BRIEF2).

The investigators propose a randomized single-blind comparative effectiveness trial of AT vs DISE-directed sleep surgery for the treatment of OSA in children with DS (Figure 4). The investigators' primary hypothesis is that a personalized surgical intervention based on DISE findings will be more effective in treating OSA in children with DS than the standard AT. The first aim will compare the change in the obstructive apnea-hypopnea index (oAHI) between these treatment arms, and the second aim will compare the change in subjective measures of sleep apnea related quality of life (OSA-18) and executive function (BRIEF2). Outcomes will be assessed 6 months after surgery. The trial will be conducted at seven sites: Oregon Health and Science University, Cincinnati Children's Hospital and Medical Center, University of Michigan, University of Texas-Southwestern, Eastern Virginia Medical School, Texas Children's, and Children's Hospital Colorado.

Conditions

Obstructive Sleep Apnea; Down Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

DISE-Directed Surgery

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

Adenotonsillectomy

Intervention Type: PROCEDURE

Tonsil and adenoid removal

Interventions

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.

Intervention Type: PROCEDURE

Adenotonsillectomy

Tonsil and adenoid removal

Intervention Type: PROCEDURE

Other Intervention Names

AT

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

University of Texas

OTHER

Sponsor Role: collaborator

Eastern Virginia Medical School

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Texas Children's

UNKNOWN

Sponsor Role: collaborator

Children's Hospital Colorado

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Derek Lam, MD, MPH

Associate Professor of Otolaryngology - Head and Neck Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Derek Lam, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Colorado Children's Hospital

Aurora, Colorado, United States

Site Status: NOT_YET_RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status: ACTIVE_NOT_RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status: RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status: NOT_YET_RECRUITING

EVMS Medical School

Norfolk, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Eleni O'Neill

Role: CONTACT

topsds@ohsu.edu

503-875-9895

Derek Lam, MD

Role: CONTACT

lamde@ohsu.edu

503-494-9419

Facility Contacts

Kristi Engle Folchert

Role: primary

KRISTI.ENGLEFOLCHERT@CUANSCHUTZ.EDU

Brittany Nordhaus

Role: primary

nbrittan@med.umich.edu

Maelyn Fulton

Role: backup

maelyn@med.umich.edu

Eleni O'Neill

Role: primary

topsds@ohsu.edu

503-875-9895

Claudia Rivera

Role: primary

Claudia.Rivera2@UTSouthwestern.edu

Francesca Chambers

Role: backup

Francesca.Chambers@UTSouthwestern.edu

Aaron Martinez

Role: primary

axmart26@texaschildrens.org

Marysha Jones

Role: primary

JonesMJ@evms.edu

Lucky Enugu

Role: backup

enugul@evms.edu

Other Identifiers

1R61HL165345

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00024746

Identifier Type: -

Identifier Source: org_study_id