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

Obstructive Sleep Apnea Clinical Trial

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

Status Enrolling by invitation

Clinical Trial 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.

Clinical Trial 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 obesity 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 five sites: Oregon Health and Science University, Cincinnati Children's Hospital and Medical Center, University of Michigan, University of Texas-Southwestern, and Eastern Virginia Medical School. ;

Related Conditions & MeSH terms

• Apnea
• Down Syndrome
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Syndrome

• NCT number: NCT05508971
• Study type: Interventional
• Source: Oregon Health and Science University
• Status: Enrolling by invitation
• Phase: N/A
• Start date: August 23, 2023
• Completion date: June 30, 2027