Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea

(CRESCENT Trial)

Overseen By Otolaryngology Research Group

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Must not be taking: Opiates

Disqualifiers: Pregnancy, Shift work, Cardiopulmonary, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called hypoglossal nerve stimulation (HGNS) for individuals with obstructive sleep apnea (OSA), a condition that causes breathing to stop and start during sleep. The goal is to determine if this therapy can reduce the risk of heart and metabolism problems associated with OSA. Participants will have their HGNS therapy either turned on or off to compare the effects. Those who have used HGNS therapy successfully for at least three months and experience frequent breathing interruptions during sleep might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance the understanding and treatment of OSA.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who use opiate medications regularly.

What prior data suggests that hypoglossal nerve stimulation therapy is safe for treating obstructive sleep apnea?

Research has shown that hypoglossal nerve stimulation (HGNS) therapy is generally safe for treating obstructive sleep apnea (OSA). Studies indicate that patients usually tolerate the therapy well, with most side effects occurring around the time of device implantation. These side effects are typically not serious.

One study found that most patients are satisfied with the treatment and continue using it. So far, HGNS therapy has proven to be safe, making it a promising option for those with sleep apnea. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Hypoglossal Nerve Stimulation (HGNS) therapy for obstructive sleep apnea because it offers a unique approach compared to traditional treatments like CPAP machines and oral appliances. Unlike these standard treatments that work externally or mechanically, HGNS is an implantable device that stimulates the hypoglossal nerve to keep the airway open during sleep. This method uses the body's own muscles to maintain airflow, which could lead to better comfort and adherence for patients. Additionally, HGNS is personalized through therapeutic voltage settings confirmed during an overnight sleep study, potentially providing more effective and tailored treatment outcomes.

What evidence suggests that hypoglossal nerve stimulation is effective for obstructive sleep apnea?

Research has shown that stimulating the hypoglossal nerve (HGNS) can effectively treat obstructive sleep apnea (OSA). In this trial, participants will either continue with their therapeutic HGNS (HGNS-on) or have the HGNS therapy turned off (HGNS-off) to mimic untreated OSA. Studies have found that HGNS can lower the apnea-hypopnea index (AHI), which measures the severity of sleep apnea, by more than 20 points. This reduction means fewer breathing interruptions during sleep. Patients have also reported a better quality of life and improved results in sleep studies. Although one study did not find significant changes in heart-related measures, HGNS remains a safe and effective way to manage moderate to severe OSA. Long-term benefits have been noted, making HGNS a promising treatment for many people. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep. Participants should be interested in seeing if turning off their hypoglossal nerve stimulation (HGNS) therapy affects metabolism and inflammation.

Inclusion Criteria

I haven't used any treatments for sleep apnea for at least a month before my HGNS surgery.

I have been using HGNS therapy for over 3 months, at least 20 hours a week recently.

Exclusion Criteria

Inability to provide informed consent

I am pregnant or planning to become pregnant.

Shift workers, heavy machinery operators, or unable to avoid driving during the study (e.g. commercial drivers)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

HGNS-off Phase

Participants will have their HGNS therapy turned off to mimic untreated OSA

2-4 weeks

Multiple visits for assessments

HGNS-on Phase

Participants will continue with their therapeutic HGNS therapy

2-4 weeks

Multiple visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hypoglossal Nerve Stimulation Therapy

Trial Overview The study tests the effects of not using HGNS therapy, which typically helps keep airways open during sleep for OSA patients. It aims to understand how stopping this treatment might change metabolic health and inflammation levels.

How Is the Trial Designed?

Group I: No HGNS therapy (HGNS-off) Experimental Treatment 1 Intervention

HGNS therapy will be turned off by the participant for this arm of the study. This arm will mimic the participant's untreated OSA statement before they had HGNS therapy activated.

Group II: Therapeutic HGNS (HGNS-on) Active Control 1 Intervention

Prior to enrollment in this study, participants will have been implanted with and stabilized on HGNS therapy. As part of clinical care, a therapeutic voltage setting will have been confirmed via overnight sleep study. This arm of the study maintains the participants on the HGNS therapy at the therapeutic voltage they have been using. This is a representation of the patient's baseline status.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Yi Cai

Lead Sponsor

Trials

1

Recruited

60+

Triological Society

Collaborator

Trials

2

Recruited

60+

American Academy of Sleep Medicine

Collaborator

Trials

29

Recruited

3,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

Hypoglossal nerve stimulation (HNS) therapy is FDA-approved for treating moderate-to-severe obstructive sleep apnea (OSA) in patients who cannot tolerate CPAP, with specific criteria including a body mass index <32 and an apnea-hypopnea index <50.

The STAR trial demonstrated that HNS therapy can provide significant therapeutic benefits for certain OSA patients, although the results may not apply to all individuals with OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglossal nerve stimulation for obstructive sleep apnea: A review of the literature. Wray, CM., Thaler, ER.[2022]

In a study of 76 patients with obstructive sleep apnea, hypoglossal nerve stimulation significantly improved sleep metrics, reducing the median apnea-hypopnea index from 30.0 to 18.6 events per hour and the Epworth Sleepiness Scale from 13.5 to 7.6 after 12 months.

Modifying stimulation parameters from 90 μsec at 33 Hz to 120 μsec at 40 Hz reduced the voltage needed for effective tongue protrusion, indicating a potential for optimizing treatment while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impulse Configuration in Hypoglossal Nerve Stimulation in Obstructive Sleep Apnea: The Effect of Modifying Pulse Width and Frequency. Steffen, A., Jeschke, S., Soose, RJ., et al.[2022]

Hypoglossal nerve stimulation is an effective treatment for obstructive sleep apnea (OSA), achieving over an 80% success rate in improving symptoms.

Patients using this device report high tolerance and adherence to therapy, with many preferring it over traditional continuous positive airway pressure (CPAP) therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglossal Nerve (Cranial Nerve XII) Stimulation. Yu, JL., Thaler, ER.[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]

Ultrasonographic assessment of hyoid bone excursion (HBE) during hypoglossal nerve stimulation (HGNS) programming can effectively optimize therapy for obstructive sleep apnea, as it correlates with treatment outcomes.

In a study of 17 subjects, those who responded to HGNS (showing a significant reduction in apnea hypopnea index) had greater HBE, indicating that monitoring tongue movement can help predict and enhance the efficacy of HGNS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea With Ultrasound Assessment of Tongue Movement. Korotun, M., Quintero, L., Shikowitz, M., et al.[2022]

Hypoglossal nerve stimulation (HGNS) significantly improves apnea-hypopnea indices (AHI) in patients with obstructive sleep apnea (OSA) who are intolerant to CPAP, with median AHI decreasing from 38.5 to 2.7 after treatment.

Patient characteristics such as a higher Friedman tongue position (grade IV) and Mallampati score (III/IV) were linked to a lesser response to HGNS, indicating that these measures can help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Predictors of Response to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea. Xiao, R., Trask, DK., Kominsky, AH.[2020]

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]

A review of 132 patient reports on hypoglossal nerve stimulator implantation for obstructive sleep apnea revealed 134 adverse events, including device migration and infection, leading to 32 device revisions and 17 explantations.

While hypoglossal nerve stimulators generally improve obstructive sleep apnea, complications such as pneumothorax and lead migration into the pleural space were noted, highlighting the need for thorough patient communication about potential risks during the consent process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events in Hypoglossal Nerve Stimulator Implantation: 5-Year Analysis of the FDA MAUDE Database. Bellamkonda, N., Shiba, T., Mendelsohn, AH.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38123511/

Hypoglossal Nerve Stimulation Effects on Obstructive ... HGS can enhance quality of life scores and polysomnography outcomes in obstructive sleep apnea patients.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0954611124003019

Hypoglossal nerve stimulation for obstructive sleep apnea ... Results show that HGNS is an effective and safe treatment option. The Inspire device significantly improved, reducing the apnea-hypopnea index (AHI) by −20.14 ...

3. jamanetwork.com jamanetwork.com/journals/jamaotolaryngology/fullarticle/2812536

Hypoglossal Nerve Stimulation and Cardiovascular ... In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different ...

4. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11328

How we measure hypoglossal nerve stimulator outcome matters We propose that HGNS outcomes should be assessed using full-night, single amplitude sleep studies to ensure a more accurate evaluation of HGNS therapy efficacy.

5. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=38528

LCD - Hypoglossal Nerve Stimulation for the Treatment of ... Conclusions from the 5-year outcomes were that UAS is a nonanatomic surgical treatment with long-term benefit for individuals with moderate to severe OSA who ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11313308/

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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07049744

Hypoglossal Nerve Stimulation for the Treatment of Adult ... The goal of this interventional study is to assess the safety and performance of the XII Medical Hypoglossal Nerve Stimulation (HGNS) System in people who have ...

8. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11822

Bilateral hypoglossal nerve stimulation for obstructive sleep ... Therapy efficacy and safety were assessed over 12 months in 115 participants in a prospective, multicenter clinical trial. Study Impact: The coprimary outcomes ...