Airway Opening Techniques for Obstructive Sleep Apnea

(DISE-CAD Trial)

No longer recruiting at 1 trial location

Overseen By Everett Seay

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Mri contraindications, Inspire model 3024, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how tongue muscles can help keep the airway open during sleep for those with obstructive sleep apnea. Researchers believe certain tongue muscles can prevent blockages while sleeping. Participants will receive lingual muscle stimulation, which involves stimulating tongue muscles, to see if it improves their nighttime breathing. Suitable candidates have used an Inspire hypoglossal nerve stimulator for at least two weeks and are following their treatment plan. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve sleep apnea treatments.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that these airway opening techniques are safe for obstructive sleep apnea?

Research has shown that stimulating the tongue muscles is a generally safe treatment for obstructive sleep apnea. This method activates the hypoglossal nerve, helping to keep the airway open during sleep and reducing apnea severity without waking the patient.

The treatment maintains a good safety record. Most side effects relate to the device's implantation rather than its use, and these are usually minor and manageable. Overall, patients have responded well to this treatment, making it a promising option for those who find traditional therapies like CPAP machines challenging. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about lingual muscle stimulation for obstructive sleep apnea because it offers a novel approach to treatment by directly targeting the muscles of the tongue. Unlike traditional methods like CPAP machines, which rely on continuous airflow to keep airways open, this technique focuses on strengthening the tongue muscles to prevent airway collapse during sleep. This approach could lead to a more comfortable and less intrusive alternative, potentially increasing patient compliance and improving overall quality of life.

What evidence suggests that this trial's treatments could be effective for obstructive sleep apnea?

Research shows that stimulating the hypoglossal nerve, which controls the tongue muscles, can help people with obstructive sleep apnea (OSA) breathe better while sleeping. In this trial, participants will receive Lingual Muscle Stimulation, which studies have shown significantly reduces the severity of OSA, both in sleep test results and patient-reported outcomes. This treatment is considered safe and effective, with high patient satisfaction. This method is gaining attention as an innovative way to keep the airway open during sleep. Overall, evidence supports its potential to help people with this condition. ^{5 6 7 8 9}

Who Is on the Research Team?

Raj C Dedhia, MD, MSCR

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 22 with obstructive sleep apnea who have an MRI-safe Inspire hypoglossal nerve stimulator and use it more than 20 hours a week. It's not for those with MRI contraindications, certain Inspire models, a recent sleep-related driving incident, trouble sleeping on their back or in labs, or pregnant women.

Inclusion Criteria

I have used Inspire therapy for my sleep disorder for over 20 hours a week.

You need to have Inspire remote model 2500 or a newer version.

I am 22 years old or older.

Exclusion Criteria

Pregnant women

You have had significant trouble falling or staying asleep during a sleep study.

I cannot sleep on my back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study A

Focus on measurements obtained as part of routine clinical care, including characterizing upper airway pressure-flow/area relationships during DISE and examining effects of maxillo-mandibular restriction and tongue size on upper airway functional properties.

Up to 3 months

Study B

In addition to Study A objectives, assess effects of stimulating specific lingual muscles on upper airway patency during natural sleep and drug-induced sleep.

Up to 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements of maximal pharyngeal cross-sectional area and tongue force.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Digital Morphometrics
• Lingual Muscle Stimulation
• Magnetic resonance imaging (MRI)
• Mandibular advancement
• Polysomnography (PSG) - Split Night
• Postural maneuvers
• Tongue Force Exercise

Trial Overview

The study tests how specific tongue muscles help keep the airway open during sleep using treatments like lingual muscle stimulation and tongue exercises. Techniques include MRIs to view muscles and overnight studies (PSG) to monitor sleep and breathing.

How Is the Trial Designed?

Group I: Study B - HGNS Responders Experimental Treatment 1 Intervention

Participants with implanted Inspire HGNS devices undergo DISE and overnight polysomnography to assess upper airway responses with and without HGNS stimulation. CPAP titration is performed during DISE. Upper airway MRI and tongue force assessments are also conducted. Response was defined by a ≥ 50% reduction in AHI with stimulation.

Group II: Study B - HGNS Nonresponders Experimental Treatment 1 Intervention

Participants with implanted Inspire HGNS devices undergo DISE and overnight polysomnography to assess upper airway responses with and without HGNS stimulation. CPAP titration is performed during DISE. Upper airway MRI and tongue force assessments are also conducted. Nonresponse was defined by a \< 50% reduction in AHI with stimulation.

Group III: Study A - Functional Phenotyping during DISE Active Control 1 Intervention

Participants with diagnosed OSA undergo Drug-Induced Sleep Endoscopy (DISE) to characterize determinants of upper airway obstruction using CPAP and pharyngeal manometry. Jaw thrust and other positional maneuvers are performed during DISE as part of routine clinical standard of care.

Lingual Muscle Stimulation is already approved in United States, European Union for the following indications:

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

• Obstructive Sleep Apnea

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

• Obstructive Sleep Apnea

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

The Genio™ system for bilateral hypoglossal nerve stimulation (HNS) significantly reduced the severity of obstructive sleep apnea (OSA) after 6 months, with the apnoea-hypopnoea index (AHI) decreasing from 23.7 to 12.9 events per hour (p<0.001).

Participants also reported improvements in daytime sleepiness and sleep-related quality of life, with no serious device-related adverse events occurring during the study, indicating a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea. Eastwood, PR., Barnes, M., MacKay, SG., 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]

Hypoglossal nerve stimulation is a promising treatment for obstructive sleep apnea, with a very low overall rate of serious adverse events (<2%) reported in initial trials, indicating its safety.

Despite the low complication rate, there is a risk of iatrogenic pneumothorax during the procedure, highlighting the need for surgeons to be aware of this potential issue and prepared to manage it effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iatrogenic pneumothorax during hypoglossal nerve stimulator implantation. Arteaga, AA., Pitts, KD., Lewis, AF.[2019]

The Upper Airway Stimulation (UAS) system is shown to be a safe and effective treatment for moderate to severe obstructive sleep apnea (OSA) in patients who are unable or unwilling to use CPAP, with significant improvements in apnea hypopnea index (AHI) and sleep quality measures after 6 months.

Successful therapy response was associated with specific baseline characteristics, including a body mass index (BMI) of 32 or less and an AHI of 50 or less, indicating that patient selection can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implanted upper airway stimulation device for obstructive sleep apnea. Van de Heyning, PH., Badr, MS., Baskin, JZ., et al.[2022]

In a study of 14 patients undergoing selective upper airway stimulation for obstructive sleep apnea, different tongue motions were observed post-surgery, with bilateral protrusion being the most common, which correlated with better therapy outcomes.

The average apnea-hypopnea index (AHI) significantly decreased from 32.5 before surgery to 14.1 at 6 months post-surgery, indicating that the therapy effectively reduced sleep apnea severity, particularly in patients exhibiting specific tongue movements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional outcome of tongue motions with selective hypoglossal nerve stimulation in patients with obstructive sleep apnea. Heiser, C., Maurer, JT., Steffen, A.[2022]

In a study of 30 patients with sleep apnea, hypoglossal nerve stimulation (HGNS) significantly increased airflow during sleep, demonstrating a clear dose-dependent response without waking the patients.

HGNS effectively eliminated inspiratory airflow limitation (IFL) in 57% of patients, indicating its potential efficacy in treating various severities of sleep apnea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Schwartz, AR., Barnes, M., Hillman, D., et al.[2021]

In a study of 51 patients with obstructive sleep apnea, unilateral hypoglossal nerve stimulation led to significant improvements in apnea-hypopnea index and oxygen desaturation levels, regardless of whether patients exhibited bilateral or unilateral tongue muscle activation.

About 39% of patients showed activation in both sides of the tongue muscle during stimulation, but this contralateral activation did not predict clinical outcomes, indicating that both response types can effectively improve sleep apnea symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contralateral Tongue Muscle Activation during Hypoglossal Nerve Stimulation. Sturm, JJ., Modik, O., Koutsourelakis, I., et al.[2020]

Hypoglossal nerve stimulation (HNS) is an effective new treatment for moderate to severe obstructive sleep apnea (OSA) in patients who cannot tolerate continuous positive airway pressure (CPAP), as shown in the multicenter STAR study.

The Inspire™ system for HNS significantly improves both objective and subjective measures of OSA severity by preventing pharyngeal collapse during sleep without waking the patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Upper Airway Stimulation in OSA]. Bender, B.[2018]

In a study of 13 participants with obstructive sleep apnea, those who responded positively to upper airway stimulation showed a significant reduction in their apnea-hypopnea index (AHI) by about 22.63 events per hour, while nonresponders showed no change.

The mechanism of action for effective responders included a smaller baseline soft palate volume and greater movement of the tongue and hyoid bone during stimulation, which contributed to increased airway size in the retroglossal region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea. Schwab, RJ., Wang, SH., Verbraecken, J., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4434556/

Upper Airway Stimulation for Obstructive Sleep Apnea

The trial demonstrated that hypoglossal nerve stimulation led to significant improvements in objective and subjective measurements of the severity of OSA.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0954611124003019

Hypoglossal nerve stimulation for obstructive sleep apnea ...

Hypoglossal nerve stimulation is a safe and effective treatment for patients with OSA, exhibiting high adherence and satisfaction rates.

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1308659

Upper-Airway Stimulation for Obstructive Sleep Apnea

We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea.

4.

mayoclinic.org

mayoclinic.org/medical-professionals/pulmonary-medicine/news/the-emerging-option-of-upper-airway-stimulation-therapy/mac-20431242

The emerging option of upper airway stimulation therapy

Activation of this muscle via stimulation of the hypoglossal nerve is a creative new approach for treatment of obstructive sleep apnea (OSA).

5.

uptodate.com

uptodate.com/contents/hypoglossal-nerve-stimulation-for-adult-patients-with-obstructive-sleep-apnea/print

Hypoglossal nerve stimulation for adult patients with ...

Data to support HNS are largely derived from the Stimulation Therapy for Apnea Reduction (STAR) trial, which demonstrated efficacy of HNS in select patients ...

6.

accessdata.fda.gov

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

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

The IPG detects the patient's respiratory effort and maintains airway patency with mild stimulation of the hypoglossal nerve during inspiration.

7.

accessdata.fda.gov

accessdata.fda.gov/cdrh_docs/pdf13/p130008b.pdf

summary of safety and effectiveness data (ssed)

It demonstrated that nightly stimulation in patients with moderate to severe obstructive sleep apnea markedly diminished apnea severity without arousing ...

8.

inspiresleep.com

inspiresleep.com/

Inspire Sleep Apnea Innovation - Obstructive Sleep Apnea ...

Inspire® therapy is a mask-free solution for people with obstructive sleep apnea who have tried and struggled with CPAP. No mask. No hose. Just sleep.™

9.

mdpi.com

mdpi.com/2077-0383/13/15/4282

Adverse Events with Hypoglossal Nerve Stimulation in the ...

In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation.