Personalized Surgery for Sleep Apnea in Down Syndrome

(TOPS-DS Trial)

Recruiting at 6 trial locations

Overseen By Derek Lam, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Single surgery event

303 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new, personalized surgical approach to treat sleep apnea in children with Down syndrome. Sleep apnea, which causes breathing issues during sleep, is more common and often harder to treat in these children. The trial compares the standard surgery, adenotonsillectomy (removal of tonsils and adenoids), to a customized surgery guided by sleep endoscopy, a procedure that observes the airway during sleep. The researchers aim to determine if tailoring the surgery based on individual needs improves outcomes. Children with Down syndrome who have moderate to severe sleep apnea and haven’t had previous tonsil surgery might be good candidates. As an unphased trial, this study offers the chance to contribute to innovative research that could improve treatments for children with Down syndrome.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that 31.5% of children with Down syndrome who underwent adenotonsillectomy (AT) experienced complications. Despite this, AT is typically the first treatment choice for children with obstructive sleep apnea (OSA), a condition that affects breathing during sleep. Although AT can alleviate breathing problems, about half of the children with Down syndrome continue to have OSA after surgery.

Research suggests that a personalized surgical approach using drug-induced sleep endoscopy (DISE) might be beneficial. DISE involves using a camera to identify blockages during sleep. Some small studies have shown that DISE-guided surgeries can effectively treat OSA in children with Down syndrome. This method allows doctors to plan surgeries more accurately, potentially leading to better outcomes.

Both AT and DISE-directed surgeries have been used in children with Down syndrome, each with its advantages and disadvantages. While there may be risks of complications, these procedures aim to improve breathing during sleep. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the personalized surgery approach for sleep apnea in individuals with Down syndrome because it tailors the surgical procedure to each patient's unique anatomy. Unlike standard adenotonsillectomy, which is a common first-line treatment removing adenoids and tonsils, this approach uses Drug-Induced Sleep Endoscopy (DISE) to assess the exact areas of airway obstruction during sedation. This enables surgeons to make real-time decisions and perform only the necessary procedures based on DISE findings. This personalized method could potentially improve outcomes by ensuring that each patient receives the most effective intervention for their specific condition.

What evidence suggests that this trial's treatments could be effective for sleep apnea in children with Down syndrome?

Research shows that removing the tonsils and adenoids (adenotonsillectomy or AT) is usually the first treatment for obstructive sleep apnea (OSA) in children. However, it is less effective for children with Down syndrome, as studies indicate that 48 to 95% of these children still have OSA after AT. In this trial, one group of participants will undergo adenotonsillectomy, while another group will receive a personalized surgery approach using drug-induced sleep endoscopy (DISE). DISE allows doctors to identify the exact location of airway blockage and tailor the surgery to each child's needs. Small studies have demonstrated that surgery guided by DISE can effectively treat OSA in children with Down syndrome. This method aims to improve results by addressing the specific causes of airway blockage in each child. ^{6 7 8 9 10}

Who Is on the Research Team?

Derek Lam, MD, MPH

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Adenotonsillectomy
• DISE-Directed Surgery

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Texas Children's

Collaborator

Trials

2

Recruited

270+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Eastern Virginia Medical School

Collaborator

Trials

77

Recruited

16,500+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

In a study of 16 patients with Down syndrome, tonsillectomy and adenoidectomy effectively relieved symptoms of upper airway obstruction in 69% of cases, indicating its efficacy for treating obstructive sleep apnea.

Postoperative complications included significant apnea, with 25% of patients requiring intensive care observation and over 60% needing supplemental oxygen, highlighting the importance of careful monitoring after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tonsillectomy and adenoidectomy in patients with Down syndrome. Bower, CM., Richmond, D.[2019]

In a study of 24 children with Down Syndrome and obstructive sleep apnea who underwent drug-induced sleep endoscopy (DISE)-directed surgery, improvements were noted in all polysomnography (PSG) parameters, indicating potential benefits of this surgical approach.

The most significant improvement was observed in the oxygen nadir for children who had previously undergone adenotonsillectomy, suggesting that DISE-directed surgery can enhance oxygen levels during sleep in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does drug induced sleep endoscopy-directed surgery improve polysomnography measures in children with Down Syndrome and obstructive sleep apnea? Akkina, SR., Ma, CC., Kirkham, EM., et al.[2019]

In a study of 56 children with obstructive sleep apnea (OSA), those who underwent drug-induced sleep endoscopy (DISE)-directed surgery showed a significant improvement in their obstructive Apnea-Hypopnea Index (oAHI), with 54% achieving an oAHI of less than 5 events per hour post-surgery.

The study found that while various surgical procedures were performed, only the race of the children (specifically white race) was a significant predictor of achieving a successful outcome (oAHI <5) after the surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Drug-Induced Sleep Endoscopy-Directed Surgery for Pediatric Obstructive Sleep Apnea. He, S., Peddireddy, NS., Smith, DF., et al.[2019]

In a study of five children with Down syndrome suffering from obstructive sleep apnea, it was found that their altered anatomy contributed to the condition, particularly affecting the oropharynx, cranium, and midface.

A modified pharyngopalatal surgical approach was effective in relieving upper airway obstruction in these patients, suggesting that traditional tonsillectomy and adenoidectomy may not be sufficient for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obstructive sleep apnea in Down syndrome children: a surgical approach. Strome, M.[2022]

In a study of children with small tonsils, DISE-directed surgery significantly improved the apnea-hypopnea index (AHI) from an average of 14.4 to 8.0, indicating better sleep apnea outcomes after surgery.

The most common surgical intervention performed was supraglottoplasty, highlighting its importance in treating sleep apnea in this population, while adenotonsillectomy was rarely used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polysomnography outcomes in children with small tonsils undergoing drug-induced sleep endoscopy-directed surgery. Miller, C., Kirkham, E., Ma, CC., et al.[2020]

Drug-induced sleep endoscopy (DISE) effectively identified tonsillar obstruction in 45.2% of pediatric obstructive sleep apnea patients with small tonsils, leading to targeted tonsillectomy in those cases.

Patients who underwent DISE-directed tonsillectomy showed significantly better long-term improvement in respiratory disturbance index (RDI) compared to controls, highlighting DISE's role in optimizing treatment decisions for OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced sleep endoscopy-directed adenotonsillectomy in pediatric obstructive sleep apnea with small tonsils. Chen, J., He, S.[2020]

In a study of 16 children with Down syndrome who had persistent obstructive sleep apnea (OSA) after adenotonsillectomy, drug-induced sleep endoscopy (DISE) effectively identified the sites of airway obstruction, allowing for targeted surgical interventions.

Post-operative results showed significant improvements in sleep apnea parameters, with 44% of the patients achieving normalization of their apnea-hypopnea index, indicating that DISE-directed treatment is a promising option for managing persistent OSA in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent Obstructive Sleep Apnea in Children with Down Syndrome After Adenotonsillectomy: Drug Induced Sleep Endoscopy-Directed Treatment. Abdel-Aziz, M., Abdel-Naseer, U., Elshahawy, E., et al.[2022]

Tonsillectomy and adenoidectomy (T&A) is effective for treating obstructive sleep apnea (OSA) in children, but about one third of cases still experience OSA after surgery, indicating a need for better pre-surgical assessment.

Drug Induced Sleep Endoscopy (DISE) may help identify additional sites of obstruction in a minority of children with OSA, particularly when clinical evaluations are inconclusive or when OSA persists post-surgery, as up to 71% of naive cases are linked to hypertrophic tonsils and/or adenoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug induced sleep endoscopy in the decision-making process of children with obstructive sleep apnea. Galluzzi, F., Pignataro, L., Gaini, RM., et al.[2022]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10698151

Treatment of Obstructive Sleep Apnea with Personalized Surgery in ... Several small case series demonstrate that personalized DISE-directed surgery can be effective in treating OSA in children with DS. Because there have been few ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05508971

Treatment of Obstructive Sleep Apnea With Personalized ... The investigators propose a randomized single-blind comparative effectiveness trial of AT vs DISE-directed sleep surgery for the treatment of OSA in children ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016558762030625X

Outcome of drug induced sleep endoscopy directed ... The literature was reviewed to determine the outcome of Drug Induced Sleep Endoscopy (DISE) directed surgery in children with obstructive sleep apnoea. Material ...

4. taggs.hhs.gov taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R33HL165345&arg_ProgOfficeCode=130

Award Information | HHS TAGGS Treatment of Obstructive Sleep Apnea with Personalized Surgery in Children with Down Syndrome ... DISE-directed surgery can be effective in treating OSA ... Data ...

5. mdpi.com mdpi.com/2227-9067/12/9/1185

Outcomes of DISE-Directed Surgery for Obstructive Sleep ... While adenotonsillectomy is the primary intervention, up to 33% of children experience residual OSA. Drug-induced sleep endoscopy (DISE) enables identification ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37226964/

A systematic review and meta-analysis In this study, we analysed the efficacy and safety of adenotonsillectomy in the treatment of children with obstructive sleep apnea and Down syndrome.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165587620305206

Morbidity and mortality from adenotonsillectomy in children ... This large single institution study evaluating morbidity and mortality following AT in children with trisomy 21 identified a morbidity rate of 31.5%.

8. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.6698

Success of Tonsillectomy for Obstructive Sleep Apnea in ... Children with DS and OSA who undergo tonsillectomy experience improvements in both respiratory event frequency and gas exchange but approximately half still ...

9. atsjournals.org atsjournals.org/doi/10.1164/rccm.202310-1857ST

Management of Persistent, Post-adenotonsillectomy ... Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/jsr.13946

Efficacy and safety of adenotonsillectomy in the ... In addition, the overall success rate was 16% (95% CI, 12%–21%) for postoperative AHI < 1 and 57% (95% CI, 51%–63%) for postoperative AHI <5.