Hypoglossal Nerve Stimulation for Down Syndrome

Not currently recruiting at 7 trial locations

Overseen By Mike Swierzewski, MS

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Inspire Medical Systems, Inc.

Must not be taking: Muscle relaxants, NSAIDs

Disqualifiers: High BMI, Autism, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the Inspire Upper Airway Stimulation (UAS) System to assist young people with Down syndrome who have moderate to severe sleep apnea. The goal is to determine if this device can enhance thinking skills and language abilities. Suitable candidates for this trial have Down syndrome, have had their tonsils and adenoids removed, and continue to experience sleep apnea despite trying other treatments like CPAP. Participants will undergo surgical implantation of the device and must be comfortable with follow-up visits and testing. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently taking muscle relaxant medication. Additionally, you should not use NSAIDs (non-steroidal anti-inflammatory drugs) for a week before and two weeks after the implantation surgery.

What prior data suggests that the Inspire Upper Airway Stimulation System is safe for adolescents and young adults with Down syndrome?

Research has shown that the Inspire Upper Airway Stimulation (UAS) System helps adults with obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep. A study in the ADHERE registry found that 91% of patients preferred the Inspire UAS over traditional CPAP machines, indicating general user satisfaction.

The FDA has approved the Inspire UAS System for adults, confirming it has passed important safety checks for that age group. Although this system is now being tested specifically for young people with Down syndrome in this trial, the previous approval for adults offers some reassurance about its safety. This trial will gather specific data on its effectiveness for adolescents and young adults with Down syndrome, as there might be differences in its effects on them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The Inspire Upper Airway Stimulation (UAS) System is unique because it offers a new approach for treating sleep apnea in individuals with Down syndrome, unlike the standard treatment of continuous positive airway pressure (CPAP). Most treatments for sleep apnea work by mechanically keeping the airway open, but Inspire UAS works differently by stimulating the hypoglossal nerve to activate the muscles that keep the airway clear. This innovative mechanism could provide a more comfortable and less intrusive alternative for patients who struggle with CPAP masks. Researchers are excited because this approach has the potential to significantly improve sleep quality and overall well-being for those with Down syndrome experiencing sleep apnea.

What evidence suggests that the Inspire UAS System is effective for sleep apnea in individuals with Down syndrome?

Research has shown that the Inspire Upper Airway Stimulation (UAS) System effectively treats obstructive sleep apnea. In earlier studies, 91% of patients preferred the Inspire UAS over traditional CPAP machines. The system addresses issues like tongue blockage, a common cause of sleep apnea. In this trial, participants with Down syndrome will receive the Inspire UAS System implant. Early results suggest the system might also enhance cognitive and language skills in teenagers with Down syndrome, offering promise for improved sleep and related mental functions in this group. ^{1 2 4 6 7}

Who Is on the Research Team?

Christopher Hartnick, MD

Principal Investigator

The Massachusetts Eye and Ear Infirmary

Are You a Good Fit for This Trial?

Adolescents and young adults aged 10-21 with Down syndrome and moderate to severe sleep apnea, post-adenotonsillectomy. They must be English-speaking, able to communicate discomfort, willing to have a permanent implant and follow-up visits. Excluded are those needing future MRI of the chest, nonverbal individuals, BMI above the 95th percentile for age, certain medical conditions or medications that increase surgery risks.

Inclusion Criteria

I am between 10 and 21 years old.

Children's parents/guardians must complete a questionnaire confirming that their child is capable of communicating feelings of pain or discomfort. They must also confirm they are able to assess their child for adverse effects related to device implantation

Two doctors approved my sleep study results within the last year.

Exclusion Criteria

I cannot have general anesthesia due to health reasons.

I am currently taking medication to relax my muscles.

I do not have any health conditions causing instability like heart failure or severe lung disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Implantation

Participants undergo implantation of the Inspire Upper Airway Stimulation (UAS) System

1 week

1 visit (in-person)

Treatment

Participants receive therapy with the Inspire UAS System and undergo follow-up visits

12 months

5 visits (in-person), including 4 in-lab sleep studies

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up assessments at 6 and 12 months post-implant

What Are the Treatments Tested in This Trial?

Interventions

• Inspire Upper Airway Stimulation (UAS) System

Trial Overview The trial is testing the Inspire Upper Airway Stimulation System in participants with Down syndrome and obstructive sleep apnea. It's a single-arm study where all enrolled will receive an implant and their cognition and language skills will be monitored over a year.

How Is the Trial Designed?

Group I: Subjects implanted with Inspire UAS System Experimental Treatment 1 Intervention

Subjects who meet eligibility criteria will be implanted with the Inspire Upper Airway Stimulation (UAS) System.

Inspire Upper Airway Stimulation (UAS) System is already approved in United States, European Union for the following indications:

Approved in United States as Inspire Upper Airway Stimulation System for:

• Moderate to severe obstructive sleep apnea in adults who are intolerant to CPAP therapy

Approved in European Union as Inspire Upper Airway Stimulation System for:

• Moderate to severe obstructive sleep apnea in adults who are intolerant to CPAP therapy

Who Is Running the Clinical Trial?

Inspire Medical Systems, Inc.

Lead Sponsor

Trials

14

Recruited

6,800+

National Institute on Deafness and Other Communication Disorders (NIDCD)

Collaborator

Trials

377

Recruited

190,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Hypoglossal nerve stimulation significantly reduces the apnea-hypopnea index by an average of 17.43 events per hour in adolescents with Down syndrome and obstructive sleep apnea, indicating its efficacy as a treatment option.

The procedure also improves quality of life, as shown by a significant reduction in the OSA-18 score, although the most common side effect reported was pain or discomfort in the tongue or mouth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglossal nerve stimulation in adolescents with down syndrome and obstructive sleep apnea: A systematic review and meta-analysis. Liu, P., Kong, W., Fang, C., et al.[2022]

Hypoglossal nerve stimulation was found to be safe and well tolerated in a case series of 6 adolescents with Down syndrome and severe obstructive sleep apnea (OSA), with an average usage of 5.6 to 10.0 hours per night.

The treatment resulted in a significant reduction in apnea hypopnea index (AHI) by 56% to 85% at 6- to 12-month follow-up, with four patients achieving an AHI of less than 5 events per hour, indicating effective management of OSA in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea. Diercks, GR., Wentland, C., Keamy, D., et al.[2022]

Upper airway stimulation (UAS) using the Inspire II implant is an effective treatment for obstructive sleep apnea (OSA) by stimulating the hypoglossal nerve to prevent airway obstruction and improve airflow.

Clinical studies show that UAS significantly enhances sleep quality and respiratory metrics in patients with moderate-to-severe OSA, making it a viable long-term treatment option with low associated risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper Airway Stimulation Therapy. Green, KK., Woodson, BT.[2017]

Hypoglossal nerve stimulation (UAS) is an effective alternative treatment for obstructive sleep apnea (OSA) in patients who cannot tolerate continuous positive airway pressure (CPAP), which is the standard treatment.

Since its reimbursement in April 2017 for specific patients in the Netherlands, there has been a notable increase in the demand for UAS, highlighting its growing acceptance as a viable option for managing OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypoglossal nerve stimulation for obstructive sleep apnoea; technique, indication and future prospects]. Vonk, PE., Benoist, LBL., Kasius, KM., et al.[2020]

Upper airway stimulation (UAS) significantly reduced the apnea-hypopnea index (AHI) from 37.4 to 8.7 events per hour after 12 months, indicating its effectiveness in treating moderate-to-severe obstructive sleep apnea.

The treatment had a high surgical success rate of 96%, although 28% of patients reported adverse events, suggesting that while UAS is generally safe, some patients may experience complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper Airway Stimulation in Patients with Obstructive Sleep Apnea: Long-Term Surgical Success, Respiratory Outcomes, and Patient Experience. Veugen, CCAFM., Dieleman, E., Hardeman, JA., et al.[2023]

Hypoglossal nerve stimulation (HNS) with Inspire is a cost-effective treatment for patients with moderate to severe obstructive sleep apnoea who cannot tolerate CPAP, showing an incremental cost-effectiveness ratio of £17,989 per quality-adjusted life-year (QALY) gained.

Patients receiving HNS are expected to gain more quality-adjusted life years (12.72 QALYs) compared to those receiving no treatment (11.15 QALYs), indicating that HNS not only improves health outcomes but is also a financially viable option for the NHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breathing Synchronised Hypoglossal Nerve Stimulation with Inspire for Untreated Severe Obstructive Sleep Apnoea/Hypopnoea Syndrome: A Simulated Cost-Utility Analysis from a National Health Service Perspective. Blissett, DB., Steier, JS., Karagama, YG., et al.[2021]

Upper airway stimulation (UAS) of the hypoglossal nerve significantly reduced the apnea-hypopnea index (AHI) from 28.6 to 9.5 after 12 months in a study of 60 patients with moderate-to-severe obstructive sleep apnea (OSA).

Patients reported improved sleep quality, as indicated by significant enhancements in the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire, demonstrating that UAS is both a safe and effective treatment option for OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome after one year of upper airway stimulation for obstructive sleep apnea in a multicenter German post-market study. Steffen, A., Sommer, JU., Hofauer, B., et al.[2022]

Upper airway stimulation using a hypoglossal nerve stimulator shows promise as a treatment for severe obstructive sleep apnea in children with Down syndrome, highlighting its potential efficacy in this specific population.

A modified surgical technique using a single chest incision is recommended for pediatric patients with smaller body sizes, which may improve safety and outcomes during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified surgical approach to hypoglossal nerve stimulator implantation in the pediatric population. Bowe, SN., Diercks, GR., Hartnick, CJ.[2018]

The hypoglossal nerve stimulator was successfully implanted in a pediatric patient with Down syndrome and severe obstructive sleep apnea (OSA), leading to a significant reduction in apnea events from 48.5 to 3.4 events per hour.

This treatment was well tolerated by the patient, allowing for the removal of a long-standing tracheotomy five months post-implantation, demonstrating its efficacy as an alternative to continuous positive airway pressure in children who cannot tolerate conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglossal Nerve Stimulator Implantation in an Adolescent With Down Syndrome and Sleep Apnea. Diercks, GR., Keamy, D., Kinane, TB., et al.[2022]

Citations

1. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf13/P130008S090b.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) Direct assessments of patient preference between Inspire. UAS and CPAP were done in the ADHERE registry, showing 91% of patients preferred.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06851338

Pediatric Down Syndrome Post-Approval Study The purpose of this Post Approval research study is to assess ongoing safety and effectiveness of the Inspire therapy in adolescents and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04801771

Effects of Hypoglossal Nerve Stimulation on Cognition and ... The study is being conducted in order to evaluate objective change in cognition and expressive language after implant and therapy with the Inspire UAS System.

4. aao-hnsfjournals.onlinelibrary.wiley.com aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1002/ohn.1030

Cost‐Effectiveness of Hypoglossal Nerve Stimulation for ... Upper airway stimulation (UAS) (Inspire Medical Systems) has been shown to be effective in treating tongue base obstruction and is an ...

5. fda.gov fda.gov/medical-devices/recently-approved-devices/inspire-upper-airway-stimulation-p130008s090

Inspire Upper Airway Stimulation – P130008/S090 The Inspire UAS system is used to treat people with moderate to severe obstructive sleep apnea (15≤ AHI ≤ 100) who are age 22 and older and who:.

6. professionals.inspiresleep.com professionals.inspiresleep.com/en-us/indications-and-contraindications/

Indications & Contraindications Inspire Upper Airway Stimulation (UAS) is used to treat a subset of patients with moderate to severe Obstructive Sleep Apnea (OSA).

7. amerihealthcaritasdc.com amerihealthcaritasdc.com/content/dam/amerihealth-caritas/acdc/pdf/provider/resources/clinical/policies-20250711/ccp1270-hypoglossal-nerve-stimulation.pdf.coredownload.inline.pdf

Hypoglossal nerve stimulation Summary of safety and effectiveness data (SSED). P130008/S090. Implantable Upper Airway Stimulation for Obstructive Sleep Apnea (OSA). Inspire ...