Airway Opening Techniques for Obstructive Sleep Apnea

(DISE-CAD Trial)

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

133 Participants Needed

Trial Summary

What is the purpose of this trial?

The current study is designed to examine underlying mechanisms of action of lingual muscles in the maintenance of airway patency during sleep. The investigators' major hypothesis is that specific tongue muscles are responsible for relieving upper airway obstruction during sleep.

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 data supports the idea that Airway Opening Techniques for Obstructive Sleep Apnea is an effective treatment?

The available research shows that stimulating the hypoglossal nerve, which controls tongue movement, can help treat obstructive sleep apnea. This treatment helps keep the airway open during sleep by moving the tongue and other muscles in the throat. Studies have shown that this method is effective for people who can't use other common treatments like continuous positive airway pressure (CPAP). After a year of using this treatment, patients reported improvements, and tests confirmed better sleep quality. This suggests that airway opening techniques can be a successful alternative for managing sleep apnea. ^{1 2 3 4 5}

What safety data is available for airway opening techniques in treating obstructive sleep apnea?

The safety data for airway opening techniques, particularly hypoglossal nerve stimulation (HNS), indicates that it is a promising treatment for obstructive sleep apnea (OSA). Studies have shown that HNS decreases OSA severity by activating the genioglossus muscle and reducing upper airway collapsibility. The Genio™ system, a novel device for bilateral HNS, was assessed for safety and effectiveness at 6 months post-implantation. Another study reported outcomes after 12 months of upper airway stimulation, showing its implementation in routine clinical practice for patients who cannot adhere to continuous positive airway pressure. A second-generation Upper Airway Stimulation (UAS) system was examined for safety and preliminary effectiveness, with baseline predictors for therapy success identified. However, there are risks involved, such as iatrogenic pneumothorax during implantation, as noted in the Stimulation Therapy for Apnea Reduction Trial, which reported a rate of serious adverse events. ^{1 4 6 7 8}

Is Lingual Muscle Stimulation a promising treatment for Obstructive Sleep Apnea?

Yes, Lingual Muscle Stimulation, also known as Hypoglossal Nerve Stimulation, is a promising treatment for Obstructive Sleep Apnea. It helps keep the airway open during sleep by stimulating muscles in the tongue area, which prevents airway collapse. Studies have shown significant improvements in sleep quality for patients who do not tolerate standard treatments. ^{1 2 3 5 9}

Research Team

Raj C Dedhia, MD, MSCR

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

Group I: Lingual Muscle Stimulation Patients Experimental Treatment 7 Interventions

DISE

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

References

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

Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. [2021]

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

Anatomic predictors of response and mechanism of action of upper airway stimulation therapy in patients with obstructive sleep apnea. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Functional outcome of tongue motions with selective hypoglossal nerve stimulation in patients with obstructive sleep apnea. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Contralateral Tongue Muscle Activation during Hypoglossal Nerve Stimulation. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea. [2021]

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

Implanted upper airway stimulation device for obstructive sleep apnea. [2022]

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

Iatrogenic pneumothorax during hypoglossal nerve stimulator implantation. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[Upper Airway Stimulation in OSA]. [2018]