Phrenic Nerve Stimulation for Acute Respiratory Distress Syndrome

(STARI Trial)

Recruiting at 3 trial locations

Overseen By STARI Study

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Lungpacer Medical Inc.

Disqualifiers: COPD, Pulmonary fibrosis, Severe liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Multi-center, randomized, controlled, open-label Phase 2 feasibility trial. Subjects on mechanical ventilation (MV) for acute hypoxemic respiratory failure (AHRF) with lung injury (including subjects who meet criteria for acute respiratory distress syndrome (ARDS)) will be randomized 2:1 to diaphragm neurostimulation-assisted ventilation (DNAV) using the AeroNova System plus lung-protective ventilation (Treatment) vs. lung-protective ventilation alone (Control).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment AeroNova System for Acute Respiratory Distress Syndrome?

Phrenic nerve stimulation, similar to the AeroNova System, has been shown to help patients with breathing issues by stimulating the diaphragm, allowing them to breathe without a ventilator. This technique has been effective in patients with spinal cord injuries and other conditions affecting breathing, suggesting it might also help those with Acute Respiratory Distress Syndrome. ^{1 2 3 4 5}

Is phrenic nerve stimulation generally safe for humans?

Phrenic nerve stimulation has been studied for conditions like central sleep apnea and spinal cord injuries, showing it can be used safely over long periods. However, it can sometimes cause unwanted stimulation, which may be uncomfortable for patients. ^{1 2 6 7 8}

How does the treatment AeroNova System for Acute Respiratory Distress Syndrome differ from other treatments?

The AeroNova System uses phrenic nerve stimulation to help the diaphragm contract, which is different from traditional treatments that rely on mechanical ventilation. This method can potentially reduce the need for mechanical ventilators by directly stimulating the nerves that control breathing, offering a novel approach to managing respiratory distress. ^{1 3 4 5 9}

Research Team

Ewan Gohligher, MD, PhD, FRCPC

Principal Investigator

Toronto General Hospital

Eligibility Criteria

This trial is for adults (18+) in the ICU who need mechanical ventilation due to severe lung issues like ARDS. They must have had acute respiratory symptoms within the last two weeks and be expected to require ventilation for at least 48 hours post-enrollment. Those not triggering the ventilator spontaneously for 2 hours prior and without plans to switch to assisted breathing can join.

Inclusion Criteria

My doctor thinks I will need help breathing with a machine for at least 2 days after joining.

I haven't needed help breathing from a machine in the last 2 hours.

I started having new breathing problems within the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive diaphragm neurostimulation-assisted ventilation using the AeroNova System plus lung-protective ventilation or lung-protective ventilation alone

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AeroNova System

Trial Overview The study tests phrenic nerve stimulation using the AeroNova System alongside standard lung-protective ventilation against just lung-protective ventilation. It's a Phase 2 trial where patients are randomly assigned in a ratio of 2:1 to either treatment or control groups.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Treatment group subjects will have the Catheter placed percutaneously into the left jugular vein or left subclavian vein. Mapping will identify the electrodes that stimulate the phrenic nerves and enable diaphragm contraction using the AeroNova Console. The stimulation level will be titrated to target a level of diaphragm activation equivalent to resting quiet breathing by adjusting the stimulation frequency and amplitude. Subjects will receive continuous stimulation plus standard of care lung-protective ventilation.

Group II: Control Active Control 1 Intervention

Standard of Care - Lung-protective ventilation

Who Is Running the Clinical Trial?

Lungpacer Medical Inc.

Lead Sponsor

Trials

8

Recruited

440+

Findings from Research

A new minimally invasive method for repositioning coronary sinus electrodes in patients with phrenic nerve stimulation (PNS) after cardiac resynchronization therapy was found to be safe and effective, with no pericardial effusion detected post-operation.

In a study of nine patients, the procedure successfully eliminated PNS in most cases, with stable pacing parameters maintained during a follow-up period of about 7.7 months, indicating a reduced burden on patients compared to traditional repositioning methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation. Szilágyi, S., Merkely, B., Zima, E., et al.[2014]

Phrenic nerve stimulation (PNS) significantly protects against diaphragm dysfunction caused by mechanical ventilation (MV) in a study involving 21 rats, restoring diaphragm function and counteracting negative gene expression changes.

While mechanical ventilation led to impaired diaphragm contractility and reduced levels of insulin-like growth factor-1 (IGF-1), PNS was able to reverse these effects, suggesting a potential therapeutic role for PNS in patients requiring mechanical ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats. Yang, M., Wang, H., Han, G., et al.[2016]

References

1. Thailand pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation for diaphragmatic pacing in a patient with high cervical spinal cord injury. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation. [2014]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Respiratory neuromodulation in patients with neurological pathologies: for whom and how? [2018]

4. Scotland pubmed.ncbi.nlm.nih.gov

Phrenic nerve stimulation: the Australian experience. [2011]

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

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragm dysfunction in rats. [2016]

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

Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Transvenous phrenic nerve stimulation for the treatment of central sleep apnea reduces episodic hypoxemic burden. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Occurrence of phrenic nerve stimulation in cardiac resynchronization therapy patients: the role of left ventricular lead type and placement site. [2012]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Phrenic Nerve Stimulation: Technology and Clinical Applications. [2015]