STIMIT Activator 1 for Diaphragm Dysfunction

Recruiting at 4 trial locations

Overseen By Tsiry Rabemahefa

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stimit AG

Must not be taking: Neuromuscular blockers

Disqualifiers: Severe COPD, Metallic implants, 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: Unknown

Duration: Up to 10 days

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the STIMIT Activator 1, a device designed to assist patients with diaphragm dysfunction who have been on a ventilator for up to 48 hours and are expected to need it for at least another 48 hours. The trial aims to determine if the device safely and effectively stimulates the diaphragm, potentially improving breathing and reducing the duration of mechanical ventilation. Participants will either receive the device or be in a control group receiving standard care. Ideal candidates have been on a ventilator for up to 48 hours and are expected to need it longer, but should not have certain medical devices, severe lung conditions, or other specific health issues.

As an unphased trial, this study allows patients to contribute to innovative research that could enhance future care for those on ventilators.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on continuous infusion of neuromuscular blocking agents, you may not be eligible to participate.

What prior data suggests that the STIMIT Activator 1 System is safe for treating diaphragm dysfunction?

Research shows that the STIMIT Activator 1 is generally safe for people. Studies have examined its effectiveness and safety for patients needing ventilator support. This treatment gently stimulates the phrenic nerve, enhancing the diaphragm's function.

One study found this nerve stimulation safe for patients, whether awake or under anesthesia. No major side effects occurred, indicating that the device does not cause serious harm. This is encouraging for those considering joining a trial, as it highlights the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for diaphragm dysfunction, which often involve mechanical ventilation or surgical interventions, the STIMIT Activator 1 offers a non-invasive approach. This device provides targeted stimulation to the phrenic nerve, which directly activates the diaphragm. Researchers are excited about this method because it has the potential to enhance diaphragm function without the need for invasive procedures or prolonged mechanical support, potentially leading to quicker recovery and improved quality of life for patients.

What evidence suggests that the STIMIT Activator 1 is effective for diaphragm dysfunction?

Research shows that the STIMIT Activator 1 aids diaphragm movement by gently stimulating a connected nerve, without surgery. In a study with critically ill patients requiring mechanical ventilation, 40.5% experienced diaphragm problems, often worsening their condition. In this trial, participants in the Stimulation Group will receive non-invasive phrenic nerve stimulation using the STIMIT device. This aims to enhance diaphragm function, potentially improving breathing and reducing the duration of mechanical ventilation. Early results suggest this method is both feasible and safe, potentially leading to quicker recovery for patients with diaphragm-related breathing difficulties. ^{1 2 3 4 6}

Who Is on the Research Team?

Laurent Brochard, MD

Principal Investigator

St Michael's Hospital Unity Health Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 21 who have been on a mechanical ventilator for up to 48 hours and are expected to need it for at least another 48 hours. They must be able to give written consent themselves or through a legal representative.

Inclusion Criteria

Informed consent in writing from patient or the legally authorized representative

I am 21 years old or older.

I have been on a breathing machine for less than 2 days and expected to need it for at least 2 more days.

Exclusion Criteria

Any patients with ICP probe

I have severe chronic lung disease.

Patients with metallic device implants or body penetrating metallic devices in the upper body area within 30cm (12inches) from the coils; known anatomy or devices in the neck area (e.g., ECMO cannulas in the neck area, collars or cranial appliances) that would interfere with headset placement or stimulation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive non-invasive stimulation of the phrenic nerve for activation of the diaphragm

Up to 10 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 days or until extubation

What Are the Treatments Tested in This Trial?

Interventions

• STIMIT Activator 1

Trial Overview The STIMIT Activator 1 System is being tested in this study. It's designed to help patients with diaphragm dysfunction who require prolonged mechanical ventilation. The study compares the safety and performance of this system against standard care in several medical centers.

How Is the Trial Designed?

Group I: Stimulation Group Experimental Treatment 1 Intervention

The intervention group will receive non-invasive stimulation of the phrenic nerve for activation of the diaphragm.

Group II: Control Group Active Control 1 Intervention

The control group will not received intervention and will be treated with standard of care.

STIMIT Activator 1 is already approved in United States, Canada for the following indications:

Approved in United States as STIMIT Activator 1 for:

• Prevention of diaphragmatic dysfunction/atrophy in mechanically ventilated patients

Approved in Canada as STIMIT Activator 1 for:

• Prevention of diaphragmatic dysfunction/atrophy in mechanically ventilated patients

Who Is Running the Clinical Trial?

Stimit AG

Lead Sponsor

Trials

5

Recruited

70+

Published Research Related to This Trial

In a study of 126 critically ill patients on mechanical ventilation, 40.5% experienced diaphragmatic dysfunction, which was linked to worse outcomes such as increased risk of pneumonia, extubation failure, longer ventilation duration, and higher mortality rates.

Early amino acid intake within the first 24 hours of ICU admission was identified as a significant modifiable risk factor that may reduce the incidence of diaphragmatic dysfunction by 29% and potentially lower mortality by 49%, highlighting its importance in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study. Pu, H., Doig, GS., Lv, Y., et al.[2023]

Diaphragm dysfunction, often caused by unilateral paralysis, can significantly impair breathing, reducing ventilatory function by about 25% in adults.

This review examines the effectiveness of diaphragm plication techniques using sutures versus staples, aiming to identify any clinical advantages of one method over the other in treating eventration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stapled Diaphragmatic Plication: Is It Better Than Suture Plication? Hill, TM., Onugha, O.[2020]

A Phase I clinical trial involving 32 mechanically ventilated children with acute respiratory distress syndrome showed that a computerized decision support tool for ventilator management was accepted over 75% of the time, indicating its feasibility in clinical practice.

Patients using the real-time effort-driven ventilator management had significantly better outcomes, including 6 more ventilator-free days and a shorter duration on mechanical ventilation compared to historical controls, without increasing the rate of reintubation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Time Effort Driven Ventilator Management: A Pilot Study. Hotz, JC., Bornstein, D., Kohler, K., et al.[2022]

In a controlled trial involving 66 ICU patients, transcutaneous electrical stimulation of the diaphragm (TEDS) did not significantly prevent diaphragmatic dysfunction or improve respiratory muscle strength compared to sham stimulation during mechanical ventilation.

Measurements of diaphragm thickening fraction, maximal inspiratory muscle pressure, and peak cough flow showed no meaningful differences between the TEDS and sham groups, indicating that TEDS may not be an effective intervention for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous electrical diaphragmatic stimulation in mechanically ventilated patients: a randomised study. Medrinal, C., Machefert, M., Lamia, B., et al.[2023]

Diaphragm pacing (DP) was successfully used in a prospective study involving 27 patients with diaphragm dysfunction, leading to substantial respiratory improvements in 62% of those implanted, indicating its potential as an effective treatment option.

This study highlights that DP can benefit patients with various causes of diaphragm dysfunction, suggesting a broader application beyond its initial indications for spinal cord injury and amyotrophic lateral sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended use of diaphragm pacing in patients with unilateral or bilateral diaphragm dysfunction: a new therapeutic option. Onders, RP., Elmo, M., Kaplan, C., et al.[2022]

Critically ill patients often experience significant diaphragm weakness, particularly those on mechanical ventilation or suffering from sepsis, which can lead to poor clinical outcomes and difficulties in weaning off ventilator support.

The review highlights that diaphragm dysfunction is linked to shared molecular mechanisms in both mechanical ventilation and sepsis, suggesting potential therapeutic targets for preventing or treating diaphragm weakness in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diaphragm Weakness in the Critically Ill: Basic Mechanisms Reveal Therapeutic Opportunities. Petrof, BJ.[2019]

In a study of 112 mechanically ventilated ICU patients, diaphragm thickness and excursion were not correlated with diaphragm function measured by phrenic nerve stimulation at the start of mechanical ventilation, indicating these measures may not be reliable indicators of diaphragm strength.

However, as patients switched to pressure support ventilation, the thickening fraction (TFdi) showed a strong correlation with diaphragm function, and a TFdi of less than 29% was effective in identifying diaphragm dysfunction, which was linked to longer ICU stays and higher mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound evaluation of diaphragm function in mechanically ventilated patients: comparison to phrenic stimulation and prognostic implications. Dubé, BP., Dres, M., Mayaux, J., et al.[2022]

In a study involving 30 adult male rats, high tidal volume mechanical ventilation was found to significantly increase TLR4 and TNF-α expression in diaphragm tissues, leading to decreased muscle contraction.

The results suggest that targeting TLR4 signaling could be a potential strategy for preventing and treating diaphragm dysfunction caused by mechanical ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TLR4 signaling is activated in ventilator-induced diaphragm dysfunction in rats. Liu, P., Zhang, H., Hu, K., et al.[2020]

In a study of 69 critically ill patients on mechanical ventilation, it was found that 50% did not resume minimal diaphragm activity within the first 24 hours, indicating a common issue of diaphragm inactivity during early mechanical ventilation.

The use of sedative agents, particularly propofol and fentanyl, was identified as a significant factor delaying the resumption of diaphragm electrical activity, regardless of the patient's overall illness severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients. Sklar, MC., Madotto, F., Jonkman, A., et al.[2021]

Diaphragmatic dysfunction, which can arise from various causes like surgery or trauma, is a significant but often overlooked contributor to respiratory issues, typically identified through chest radiography showing diaphragm elevation.

Functional imaging techniques such as fluoroscopy, ultrasonography, or MRI are effective for diagnosing types of diaphragmatic dysfunction, including paralysis, weakness, and eventration, with treatment options like plication and phrenic nerve stimulation tailored to the underlying cause and severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of the diaphragm: anatomy and function. Nason, LK., Walker, CM., McNeeley, MF., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12153206/

STIMIT ACTIVATOR 1 pivotal trial - PMC - PubMed Central - NIH The STIMIT ACTIVATOR trial is a randomized multi-center study powered to elucidate whether non-invasive phrenic nerve stimulation is feasible, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05883163

NCT05883163 | STIMIT Activator 1 IDE Pivotal Study The objective of this clinical investigation is to evaluate the safety and efficacy of the STIMIT Activator 1 device in subjects on mechanical ventilation who ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40500715/

Multi-center randomized superiority clinical trial in the early ... The STIMIT ACTIVATOR trial is a randomized multi-center study powered to elucidate whether non-invasive phrenic nerve stimulation is feasible, safe, and ...

4. withpower.com withpower.com/trial/phase-diaphragm-issues-6-2023-d5e99

STIMIT Activator 1 for Diaphragm Dysfunction In a study of 126 critically ill patients on mechanical ventilation, 40.5% experienced diaphragmatic dysfunction, which was linked to worse outcomes such as ...

5. researchgate.net researchgate.net/publication/392596888_Multi-center_randomized_superiority_clinical_trial_in_the_early_phase_of_mechanically_ventilated_patients_to_preserve_diaphragm_thickness_using_non-invasive_magnetic_phrenic_nerve_stimulation_STIMIT_A

(PDF) Multi-center randomized superiority clinical trial in ... The STIMIT ACTIVATOR trial is a randomized multi-center study powered to elucidate whether non-invasive phrenic nerve stimulation is feasible, safe, and ...

6. liebertpub.com liebertpub.com/doi/10.4187/respcare.10568

Safety and Feasibility of Noninvasive Electromagnetic ... Noninvasive repetitive electromagnetic stimulation is safe, feasible, and effective to stimulate the phrenic nerves in both awake individuals and anesthetized ...