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

Trial Summary

What is the purpose of this trial?

The purpose of this feasibility study is to assess whether an alternative transvenous lead location affects respiration and airway physiology during a commercial remedē® System or commercial transvenous cardiac device (de novo pacemaker or implantable cardiac defibrillator) implant procedure.

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 data supports the effectiveness of the treatment Transvenous Nerve Stimulation for Sleep Apnea?

Research shows that transvenous phrenic nerve stimulation (TPNS) is effective in treating central sleep apnea, with significant improvements in sleep quality and reduced sleep apnea episodes. In a study, 67% of patients experienced a 50% or greater reduction in sleep apnea events after 12 months of therapy, and improvements in quality of life were sustained. ^{1 2 3 4 5}

Is transvenous phrenic nerve stimulation safe for humans?

Transvenous phrenic nerve stimulation, used in the remedē System for treating central sleep apnea, has been shown to be generally safe in humans, with a serious adverse event occurring in 9% of patients within 12 months. The system has been approved by the FDA, and long-term safety data up to five years post-implant have been collected. ^{1 2 3 4 6}

How does transvenous nerve stimulation differ from other treatments for sleep apnea?

Transvenous nerve stimulation (TPNS) is unique because it involves implanting a device that stimulates the phrenic nerve to activate the diaphragm, improving breathing during sleep. This approach is different from other treatments like CPAP machines, which use air pressure to keep airways open, as TPNS directly targets the nerve controlling breathing. ^{1 2 3 4 6}

Research Team

Kathy A McPherson, RN, MSN

Principal Investigator

Respicardia, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes. [2023]

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

Sustained 12 Month Benefit of Phrenic Nerve Stimulation for Central Sleep Apnea. [2019]

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

Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices. [2021]

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

First interventional exchange of a left transvenous phrenic nerve stimulation lead from the novel remedē system. [2021]

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

Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea: A Pooled Cohort Analysis. [2023]

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

Meta-analysis of Usefulness of Phrenic Nerve Stimulation in Central Sleep Apnea. [2020]