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

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}

Research Team

Derek Lam, MD, MPH

Principal Investigator

Oregon Health and Science University

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.

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
• 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.

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

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+

Findings from Research

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]

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 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 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]

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]

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 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 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]

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]

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

Outcomes of Drug-Induced Sleep Endoscopy-Directed Surgery for Pediatric Obstructive Sleep Apnea. [2019]

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]

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

Polysomnography outcomes in children with small tonsils undergoing drug-induced sleep endoscopy-directed surgery. [2020]

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

Drug induced sleep endoscopy in the decision-making process of children with obstructive sleep apnea. [2022]

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

Drug-induced sleep endoscopy-directed adenotonsillectomy in pediatric obstructive sleep apnea with small tonsils. [2020]

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

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

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

Tonsillectomy and adenoidectomy in patients with Down syndrome. [2019]