Transvenous Nerve Stimulation for Sleep Apnea

Recruiting at 2 trial locations

Overseen By Morgan Battiste

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Respicardia, Inc.

Must not be taking: Muscle relaxants

Disqualifiers: Pregnancy, BMI > 40, 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: 1

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called transvenous nerve stimulation to determine its effectiveness for individuals with moderate to severe central sleep apnea. Researchers aim to discover if placing the treatment in a different part of the body can enhance breathing and airway function during a specific heart device implant procedure, such as a pacemaker. The study seeks participants with moderate to severe central sleep apnea who are scheduled to receive a remedē® System (a type of transvenous nerve stimulation) or another transvenous cardiac device. As an unphased trial, it offers participants the chance to contribute to pioneering research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking muscle relaxants, you may need approval from the site implanter and ZOLL Respicardia clinical staff to continue.

What prior data suggests that transvenous nerve stimulation is safe for sleep apnea?

Research has shown that transvenous nerve stimulation is generally safe for people. Studies have found that this method effectively treats central sleep apnea, a condition where breathing stops and starts during sleep, and is well-tolerated over time. Specifically, a five-year study confirmed that this treatment remains safe while improving sleep quality and reducing daytime tiredness. Participants did not experience major harmful side effects, and their overall sleep health improved. These findings suggest that transvenous nerve stimulation is a reliable and safe option for managing sleep apnea. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for sleep apnea, which often include CPAP machines or oral appliances, transvenous nerve stimulation offers a totally different approach. This technique involves stimulating specific nerves through a minimally invasive procedure, which could enhance breathing patterns during sleep without the need for bulky equipment. Researchers are excited because this method could provide a more comfortable and convenient alternative, potentially improving adherence and overall quality of life for patients with sleep apnea.

What evidence suggests that transvenous nerve stimulation might be an effective treatment for sleep apnea?

Research has shown that transvenous nerve stimulation, the treatment participants in this trial will receive, can greatly improve sleep apnea symptoms. Studies have found that this treatment helps people sleep better and feel less tired during the day, even up to five years after treatment. It gently stimulates a nerve that controls breathing during sleep. Many patients report better sleep and improved quality of life due to this treatment. Multiple studies support the effectiveness of transvenous nerve stimulation, highlighting its potential as a reliable way to manage sleep apnea. ^{1 3 6 7 8}

Who Is on the Research Team?

Kathy A McPherson, RN, MSN

Principal Investigator

Respicardia, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with moderate to severe central sleep apnea who are getting a new remedē® System or other cardiac device like a pacemaker. They must be able to consent and not have significant upper airway issues, nerve problems affecting the tongue, prior neck surgery, BMI over 40, unstable health conditions, pregnancy plans, dye allergies that can't be managed, past oral cavity surgeries impacting breathing or use muscle relaxants without approval.

Inclusion Criteria

I am getting a new device implanted to help with severe sleep apnea or heart rhythm.

Subject is willing and able to give informed consent

Exclusion Criteria

Subject is known to be allergic to radio opaque dye which cannot safely be pre-treated per the investigator

I've had surgery in my mouth that could affect my breathing.

I have weakness or paralysis affecting my nerves, including my tongue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Procedure

Participants undergo a commercial remedē® System or transvenous cardiac device implant procedure to assess changes in respiration and airway physiology

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transvenous nerve stimulation

Trial Overview The Janus Feasibility Study is testing if changing where transvenous leads are placed during implant procedures of devices like the remedē® System affects breathing and airway function in patients with sleep apnea.

How Is the Trial Designed?

Group I: Transvenous nerve stimulation Experimental Treatment 1 Intervention

Transvenous nerve stimulation is already approved in United States, European Union for the following indications:

Approved in United States as remedē System for:

• Central Sleep Apnea (CSA)

Approved in European Union as remedē System for:

• Central Sleep Apnea (CSA)

Who Is Running the Clinical Trial?

Respicardia, Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

Transvenous phrenic nerve stimulation (TPNS) therapy has been shown to be safe and effective in treating central sleep apnea (CSA), with significant long-term improvements in apnea-hypopnea index (AHI) and central-apnea index (CAI) over five years, as evidenced by a study involving 53 patients from the original pivotal trial.

The therapy also led to improvements in sleep architecture and daytime sleepiness, with a notable reduction in the Epworth Sleepiness Scale score, while serious adverse events were low and did not result in long-term harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes. Costanzo, MR., Javaheri, S., Ponikowski, P., et al.[2023]

The remedē system, a fully implantable device for treating central sleep apnea, can have its leads exchanged, as demonstrated in a case involving an 81-year-old patient with a fractured lead.

The lead replacement procedure can be complex, but interventional techniques like balloon angioplasty can help successfully reimplant a new lead, highlighting the need for specialized approaches in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First interventional exchange of a left transvenous phrenic nerve stimulation lead from the novel remedē system. Gutleben, KJ., Eitz, T., Westlund, R., et al.[2021]

Transvenous phrenic nerve stimulation (PNS) significantly reduces the severity of central sleep apnea (CSA), with a median reduction of 58% in apnea-hypopnea index after 6 months, and these improvements are sustained for up to 12 months.

PNS also enhances quality of life and cardiac function in patients with concomitant heart failure, showing a significant improvement in systolic function over the same period, indicating its efficacy and safety across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea: A Pooled Cohort Analysis. Fudim, M., Spector, AR., Costanzo, MR., et al.[2023]

Transvenous phrenic nerve stimulation (TPNS) is safe for patients with heart failure who also have cardiovascular implantable electronic devices (CIEDs), with no significant safety differences observed between those with and without CIEDs during the study of 151 patients.

Both groups (with and without CIEDs) showed similar efficacy in reducing the apnea-hypopnea index (AHI) and improving quality of life, indicating that TPNS is effective regardless of the presence of CIEDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices. Nayak, HM., Patel, R., McKane, S., et al.[2021]

Transvenous neurostimulation of the phrenic nerve (PNS) significantly reduced the apnea hypopnea index by an average of 26.7 events/hour in 204 patients, indicating its efficacy in treating central sleep apnea (CSA).

PNS also led to a notable decrease in the oxygen desaturation index and arousal index, suggesting improved sleep quality; however, further large-scale randomized studies are necessary to fully assess its safety and clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of Usefulness of Phrenic Nerve Stimulation in Central Sleep Apnea. Luni, FK., Daniels, J., Link, MS., et al.[2020]

Transvenous phrenic nerve stimulation significantly improved sleep metrics and quality of life in patients with central sleep apnea, with 60% of patients achieving a ≥50% reduction in apnea-hypopnea index at 6 months and 67% at 12 months.

The treatment effects were reproducible, as 55% of former control patients also achieved similar reductions in apnea-hypopnea index after 6 months of therapy, indicating the reliability of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained 12 Month Benefit of Phrenic Nerve Stimulation for Central Sleep Apnea. Costanzo, MR., Ponikowski, P., Javaheri, S., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33953626/

Transvenous Phrenic Nerve Stimulation for Treatment of ... Conclusion: Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant. Clinical trial ...

2. cfrjournal.com cfrjournal.com/articles/revisiting-transvenous-phrenic-nerve-stimulation-central-sleep-apnoea-and-heart-failure?language_content_entity=en

Transvenous Phrenic Nerve Stimulation: Innovations in Trials The PAS confirmed that TPNS improves sleep architecture, QoL and daytime sleepiness 5 years after implantation, without any additional safety ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12400169/

Revisiting Transvenous Phrenic Nerve Stimulation in Central ... This first randomised controlled trial (RCT) demonstrated that phrenic nerve stimulation significantly improved AHI, sleep structure and QoL in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1389945723004239

Transvenous phrenic nerve stimulation for treating central ... Transvenous phrenic nerve stimulation may affect sleep microstructure · Patients on therapy appeared to have less rapid and more slow cortical activity.

5. remede.zoll.com remede.zoll.com/wp-content/uploads/RMB1852-Rev-E-remede-Clinical-Fact-Sheet.pdf

system transvenous phrenic nerve stimulation for central sleep ... TRANSVENOUS PHRENIC NERVE STIMULATION FOR CENTRAL SLEEP APNEA ... This meta-analysis compared outcomes of therapies for CSA including CPAP (7 studies), ASV (9.

6. remede.zoll.com remede.zoll.com/press-releases/zoll-announces-five-year-study-confirming-safety-efficacy-and-beneficial-effects-of-long-term-transvenous-phrenic-nerve-stimulation-the-remede-system/

ZOLL Announces Five-Year Study Confirming Safety, Efficacy ... The data show sustained safety and efficacy of transvenous phrenic nerve stimulation for the treatment of moderate to severe central sleep apnea (CSA).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8092633/

Transvenous Phrenic Nerve Stimulation for Treatment of ... Long-term TPNS safely improves CSA, sleep architecture and daytime sleepiness through 5 years post implant.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01816776

Respicardia, Inc. Pivotal Trial of the remedē System Transvenous phrenic nerve stimulation improves central sleep apnea, sleep quality, and quality of life regardless of prior positive airway pressure treatment.