Clinical trial NCT05508971: Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS)
Official title: Treatment of Obstructive Sleep Apnea With Personalized Surgery in Children With Down Syndrome (TOPS-DS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obstructive Sleep Apnea
Down Syndrome
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: University of Michigan
name: University of Texas
name: Eastern Virginia Medical School
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Texas Children's
name: Children's Hospital Colorado
First posted: 2022-08-19
Enrollment: 303
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline Polysomnography Measures: oAHI at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: AHI at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: REM AHI at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: min SpO2 at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: desat index at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: % Total Sleep Time with ETCO2 > 50 mmHg at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
measure: Change from Baseline Polysomnography Measures: Max End Tidal CO2 (ETCO2) at 6 months
timeFrame: 6 month follow up sleep study (after surgery)
Secondary outcomes:
measure: Change in Obstructive Sleep Apnea (OSA)-18 Questionnaire score
timeFrame: 6 month follow up
measure: Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire score
timeFrame: 6 month follow up
measure: Change in Generic PedsQL (Pediatric Quality of Life) Questionnaire answers
timeFrame: 6 month follow up
measure: Total Drug induced sleep endoscopy (DISE) score
timeFrame: At time of surgery
measure: Adverse Events
timeFrame: 24 hour period after surgery
measure: Change in Feeding and Swallowing Impact Survey (FSIS) Questionnaire Answers
timeFrame: 6 month follow up
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Norfolk
country: United States
facility: EVMS Medical School
state: Virginia
Study officials:
affiliation: Oregon Health and Science University
name: Derek Lam, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: