Hypoglossal Nerve Stimulation for Down Syndrome

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

57 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a prospective, single-arm study conducted under a common implant and follow-up protocol. The objective will be to follow fifty-seven (57) adolescents and young adults (10-21 years of age), with Down syndrome, moderate to severe sleep apnea, and post-adenotonsillectomy, for 12 months after undergoing implant of the Inspire Upper Airway Stimulation (UAS) System. 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.

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 data supports the effectiveness of the treatment Inspire Upper Airway Stimulation (UAS) System for Down Syndrome?

Research shows that the Inspire Upper Airway Stimulation (UAS) System, which stimulates the hypoglossal nerve, is effective in treating obstructive sleep apnea (OSA) by improving airflow and sleep quality. This treatment has been successful in patients who cannot use traditional therapies, suggesting it may also help those with Down Syndrome who experience similar sleep issues. ^{1 2 3 4 5}

Is hypoglossal nerve stimulation safe for humans?

Hypoglossal nerve stimulation has been used safely in patients with obstructive sleep apnea, with studies showing it as a generally safe treatment option. However, some patients have reported adverse events, so it's important to discuss potential risks with your doctor. ^{1 4 5 6 7}

How is the Inspire Upper Airway Stimulation System treatment different from other treatments for Down syndrome-related sleep apnea?

The Inspire Upper Airway Stimulation System is unique because it is an implantable device that stimulates the hypoglossal nerve to move the tongue forward, helping to keep the airway open during sleep. This is different from other treatments like continuous positive airway pressure (CPAP), which many patients find uncomfortable, or tracheotomy, which is more invasive. ^{3 5 7 8 9}

Research Team

Christopher Hartnick, MD

Principal Investigator

The Massachusetts Eye and Ear Infirmary

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

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 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]

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]

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]

References

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

Outcome after one year of upper airway stimulation for obstructive sleep apnea in a multicenter German post-market study. [2022]

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

Upper Airway Stimulation Therapy. [2017]

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

Modified surgical approach to hypoglossal nerve stimulator implantation in the pediatric population. [2018]

4. Switzerland 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. [2021]

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

[Hypoglossal nerve stimulation for obstructive sleep apnoea; technique, indication and future prospects]. [2020]

6. Brazil pubmed.ncbi.nlm.nih.gov

Upper Airway Stimulation in Patients with Obstructive Sleep Apnea: Long-Term Surgical Success, Respiratory Outcomes, and Patient Experience. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Hypoglossal nerve stimulation in adolescents with down syndrome and obstructive sleep apnea: A systematic review and meta-analysis. [2022]

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

Hypoglossal Nerve Stimulator Implantation in an Adolescent With Down Syndrome and Sleep Apnea. [2022]

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

Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea. [2022]