Personalized Surgery for Sleep Apnea in Down Syndrome

(TOPS-DS Trial)

Recruiting in Palo Alto (17 mi)

+4 other locations

Overseen by Derek Lam, MD, MPH

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Oregon Health and Science University

Disqualifiers: Previous tonsillectomy, Bleeding disorders, Cardiopulmonary comorbidity, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for sleep apnea in children with Down Syndrome?

Research shows that drug-induced sleep endoscopy (DISE)-directed surgery can be effective for children with Down Syndrome who have persistent sleep apnea after adenotonsillectomy. In one study, 44% of these children had their sleep apnea significantly improved after DISE-directed treatment. ^{1 2 3 4 5}

Is personalized surgery for sleep apnea in Down Syndrome generally safe for humans?

The studies suggest that drug-induced sleep endoscopy (DISE)-directed surgery, including procedures like adenotonsillectomy, is generally safe for children with obstructive sleep apnea, including those with Down Syndrome. These procedures have been performed in various studies without significant safety concerns reported. ^{1 2 3 4 6}

How is the treatment for sleep apnea in children with Down syndrome unique?

This treatment is unique because it uses drug-induced sleep endoscopy (DISE) to guide surgery, allowing doctors to identify and address specific sites of airway obstruction, which is particularly beneficial for children with Down syndrome who often have persistent sleep apnea even after standard adenotonsillectomy. ^{1 3 4 7 8}

Eligibility Criteria

This trial is for children aged 2 to 17 with Down syndrome and moderate to severe obstructive sleep apnea (OSA), who haven't had tonsil surgery before. Caregivers must be able to communicate in English or Spanish, give consent, and commit to the study's procedures. Children with significant heart/lung issues besides OSA or conditions that make surgery risky are excluded.

Inclusion Criteria

Child is not pregnant

Caregiver is primary caretaker of the child

My child is a candidate for surgery.

Exclusion Criteria

Caregiver is unwilling or unable to comply with study procedures

My child needs extra oxygen or has serious heart/lung issues besides sleep apnea.

My child cannot have surgery due to a medical condition like bleeding disorders.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either DISE-directed surgery or adenotonsillectomy (AT) for the treatment of OSA

Single surgery event

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including polysomnography and quality of life measures

6 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Adenotonsillectomy (Procedure)
• DISE-Directed Surgery (Procedure)

Trial Overview The trial tests personalized surgical treatment for OSA against the standard adenotonsillectomy (AT) in kids with Down syndrome. It uses drug-induced sleep endoscopy (DISE) to tailor surgeries based on each child's specific airway blockages during sedated sleep.

Participant Groups

Group I: Drug-Induced Sleep Endoscopy Experimental Treatment 1 Intervention

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 II: Adenotonsillectomy Active Control 1 Intervention

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.

Adenotonsillectomy is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Adenotonsillectomy for:

• Obstructive sleep apnea in children

🇪🇺 Approved in European Union as Adenotonsillectomy for:

• Obstructive sleep apnea in children

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Michigan Ann Arbor, MI

Cincinnati Children's Hospital Cincinnati, OH

UT Southwestern Medical Center Dallas, TX

EVMS Medical School Norfolk, VA

More Trial Locations

Who Is Running the Clinical Trial?

Oregon Health and Science University Lead Sponsor

University of Michigan Collaborator

Eastern Virginia Medical School Collaborator

National Heart, Lung, and Blood Institute (NHLBI) Collaborator

University of Texas Collaborator

Children's Hospital Medical Center, Cincinnati Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

Persistent Obstructive Sleep Apnea in Children with Down Syndrome After Adenotonsillectomy: Drug Induced Sleep Endoscopy-Directed Treatment. [2022] Children with down syndrome (DS) are more liable to develop obstructive sleep apnea (OSA) which is usually treated with adenotonsillectomy. However, OSA may persist in many of those patients after the procedure. The aim of this study was to assess the efficacy of drug-induced sleep endoscopy (DISE)-directed treatment in management of DS children with persistent OSA after adenotonsillectomy. Sixteen DS children with persistent OSA after adenotonsillectomy were evaluated. DISE was done in the operating theatre to identify the site of obstruction, and surgical intervention was performed according to the finding. Polysomnographic study was used pre- and post-operatively to measure the outcome. DISE revealed obstruction in different sites of the airway. DISE-directed treatment was done according to the site of obstruction. Polysomnographic study showed postoperative significant changes for all parameters. The authors achieved improvement of overall apnea-hypopnea index which was normalized in seven patients (44%). In conclusion, DISE-directed treatment is an effective procedure for persistent OSA in DS children who underwent adenotonsillectomy. However, residual obstruction in those children may be due to many characteristic features that cause narrowing of the airway.

2. England pubmed.ncbi.nlm.nih.gov

Outcomes of Drug-Induced Sleep Endoscopy-Directed Surgery for Pediatric Obstructive Sleep Apnea. [2019] Objectives To determine the effectiveness of pediatric drug-induced sleep endoscopy (DISE)-directed surgery for children with infant obstructive sleep apnea (OSA) or OSA after adenotonsillectomy. Study Design Case series with chart review. Setting Tertiary care pediatric hospital. Subjects and Methods We included 56 children undergoing DISE from October 2013 to September 2015 who underwent subsequent surgery to address OSA. The primary outcome was successful response to DISE-directed surgery based on the postoperative obstructive Apnea-Hypopnea Index (oAHI). Wilcoxon matched-pairs signed-ranks tests were used to compare polysomnography variables before and after surgery, and regression was used to model response to surgery. Results We evaluated 56 patients with a mean age of 5.9 &#177; 5.5 years (range, 0.1-17.4) and mean body mass index of 21.2 &#177; 7.9 kg/m2 (percentile, 77 &#177; 30). The most commonly performed surgical procedures were adenoidectomy (48%, n = 27), supraglottoplasty (38%, n = 21), tonsillectomy (27%, n = 15), lingual tonsillectomy (13%, n = 7), nasal surgery (11%, n = 6), pharyngoplasty (7%, n = 4), and partial midline glossectomy (7%, n = 4). Mean oAHI improved from 14.9 &#177; 13.5 to 10.3 &#177; 16.2 events/hour, with 54% (30 of 56) of children with oAHI &lt;5 and 16.1% (9 of 56) with oAHI &lt;1. There was a significant improvement in oAHI ( P = .001) and saturation nadir ( P &lt; .001) but not in time with end tidal carbon dioxide &gt;50 mm Hg ( P = .14). Multivariable modeling, controlling for age, race, body mass index, sex, and baseline polysomnography variables, revealed that white race predicted success of DISE-directed surgery. Conclusion Fifty-four percent of children with infant OSA or persistent OSA after adenotonsillectomy had oAHI &lt;5 events per hour after DISE-directed surgery. Only white race was predictive of oAHI &lt;5 events per hour.

3. England pubmed.ncbi.nlm.nih.gov

Does drug induced sleep endoscopy-directed surgery improve polysomnography measures in children with Down Syndrome and obstructive sleep apnea? [2019] Children with Down Syndrome (DS) and obstructive sleep apnea (OSA) are difficult to treat, as first line therapies may not lead to significant improvement. Drug-induced sleep endoscopy (DISE) directed surgery may be particularly beneficial for these patients.

4. United States pubmed.ncbi.nlm.nih.gov

Polysomnography outcomes in children with small tonsils undergoing drug-induced sleep endoscopy-directed surgery. [2020] The optimal surgical treatment to improve sleep apnea in children with small tonsils is not known. Drug-induced sleep endoscopy (DISE) may be useful in selecting effective surgical procedures for this patient population. This study compared polysomnography (PSG) measures before and after DISE-directed surgery in children with small tonsils. We hypothesize that DISE-directed surgery improves PSG measures in children with small tonsils. We also aimed to identify the most common surgery performed in this population.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Drug induced sleep endoscopy in the decision-making process of children with obstructive sleep apnea. [2022] Tonsillectomy and adenoidectomy (T&A) is currently recommended in children with Obstructive Sleep Apnea (OSA). However, the condition persists after surgery in about one third of cases. It has been suggested that Drug Induced Sleep Endoscopy (DISE) may be of help for planning a more targeted and effective surgical treatment but evidence is yet weak. The aim of this review is to draw recommendation on the use of DISE in children with OSA. More specifically, we aimed at determine the proportion of cases whose treatment may be influenced by DISE findings. A comprehensive search of articles published from February 1983 to January 2014 listed in the PubMed/MEDLINE databases was performed. The search terms used were: "endoscopy" or "nasoendoscopy" or "DISE" and "obstructive sleep apnea" and "children" or "child" or "pediatric." The main outcome was the rate of naive children with hypertrophic tonsils and/or adenoids. The assumptions are that clinical diagnosis of hypertrophic tonsils and/or adenoids is reliable and does not require DISE, and that exclusive T&A may solve OSA in the vast majority of cases even in the presence of other concomitant sites of obstruction. Five studies were ultimately selected and all were case series. The median (range) number of studied children was 39 (15-82). Mean age varied from 3.2 to 7.8 years. The combined estimate rate of OSA consequent to hypertrophic tonsils and/or adenoids was 71% (95%CI: 64-77%). In children with Down Syndrome, the combined estimated rate of hypertrophic tonsils and/or adenoids was 62% (95%CI: 44-79%). Our findings show that DISE may be of benefit in a minority of children with OSA since up to two thirds of naive cases presents with hypertrophic tonsils and/or adenoids. Its use should be limited to those whose clinical evaluation is unremarkable or when OSA persists after T&A.

6. United States pubmed.ncbi.nlm.nih.gov

Drug-induced sleep endoscopy-directed adenotonsillectomy in pediatric obstructive sleep apnea with small tonsils. [2020] The study aims to examine drug-induced sleep endoscopy (DISE) in the decision-making process of pediatric obstructive sleep apnea (OSA) patients with small tonsils. This was a retrospective study of children who underwent awake flexible endoscopy, DISE, and adenoidectomy with/without tonsillectomy at the Shanghai Children's Medical Center between 03/2015 and 12/2016. Tonsillectomy was performed for tonsillar obstruction found by DISE. Adenoidectomy was performed for all children. Cardio-pulmonary coupling (CPC) and oximetry were observed before/after surgery. The study included 126 children: 56 (44.4%) with grade 2 tonsils and 70 (55.6%) with grade 1. Mean age was 5.7±3.2 (range, 2.8-10.4) years and mean BMI of 15.7±5.5 kg/m2. Unexpectedly, DISE showed tonsillar obstruction in 57 (45.2%) children, including 44 (78.6%) with grade 2 tonsils and 13 (18.6%) with grade 1. Therefore, DISE-directed tonsillectomy was performed for 57 patients. There was an improvement in respiratory disturbance index (RDI) and oxygen saturation nadir in the DISE (P = 0.0007, P = 0.037) and control (P = 0.001, P = 0.023) groups 6 months after surgery, but RDI improvement was better in the DISE group compared with controls 1 year after surgery (P = 0.042). DISE is a good way to determine the necessity of tonsillectomy in pediatric OSA patients with small tonsils.

7. United States pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in Down syndrome children: a surgical approach. [2022] Obstructive sleep apnea is considered in five Down syndrome children. All had altered anatomy consistent with this syndrome involving the oropharynx, cranium, and midface. Based on earlier work, it was established that, except for specific isolated instances, routine tonsillectomy and adenoidectomy would not reverse obstructive respiratory patterns in this patient population. A modified pharyngopalatal surgical approach has been successful in alleviating upper airway sleep obstruction in Down syndrome.

8. Ireland pubmed.ncbi.nlm.nih.gov

Tonsillectomy and adenoidectomy in patients with Down syndrome. [2019] Tonsillectomy and adenoidectomy in patients with Down syndrome usually relieves symptoms of upper airway obstruction due to adenotonsillar hypertrophy. A retrospective review of 16 patients with Down syndrome who underwent a tonsillectomy and adenoidectomy was conducted to define early postoperative morbidity, and to evaluate the results of the procedure. Fifteen of 16 patients had upper airway obstruction manifest by adenotonsillar hypertrophy. One had adenoid hypertrophy only. Tonsillectomy and adenoidectomy (13), adenoidectomy (1), tonsillectomy (1), and UP3/adenoidectomy (1) were performed on these patients. Four patients (25%) required observation in an intensive care setting the first night. An average hospital stay of 2.1 days was noted with a range of 0 to 7 days. Significant postoperative apnea was common, and oxygen was used in over 60% of patients. Symptoms were resolved in 69% of patients at last follow up. In conclusion, tonsillectomy and adenoidectomy can be a useful procedure for children with Down syndrome and obstructive sleep apnea, however overnight hospitalization for observation and treatment of persistent apnea is appropriate.