Clinical trial NCT05238753: Electromagnetic Stimulation of the Phrenic Nerve in Critically Ill Mechanically Ventilated Patients (STIMIT-II)
Official title: Electromagnetic Stimulation of the Phrenic Nerve to Generate Contraction of the Diaphragm in Critically Ill Mechanically Ventilated Patients - a Proof-of-concept Study (STIMIT-II)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Muscle Weakness
Critical Illness
Mechanical Ventilation Complication
Keywords: VIDD
ICUAW
Muscle Weakness
Weaning
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Stimit AG
First posted: 2022-02-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 15 patients in control group, 15 patients in interventional group with sequential design in term of daily frequency of non-invasive electromagnetic phrenic nerve stimulation, i.e. starting with 5 patients with 2 stimulation per day, followed by 5 patients with 3 stimulations and 5 patients with 5 stimulations per day
Primary purpose: PREVENTION

Brief summary: Ventilator-induced diaphragmatic dysfunction is a common issue in critically ill patients. Muscle stimulation has shown to have beneficial effects in muscle groups on the extremities. A non-invasive way to stimulate the diaphragm would be the electromagnetic stimulation but it is currently unclear if that is feasible.

In this proof-of-concept trial the primary aim is to show that it is possible to induce a diaphragmatic contraction in critically ill ICU patients via an external electromagnetic stimulation of the phrenic nerve, leading to an inspiration (i) with a sufficient tidal volume (3-6 ml/kg ideal body weight) and (ii) with verifiable muscular diaphragmatic contraction through ultrasound imaging.

Detailed description: During the time of first spontaneous breathing trial 60% of mechanically ventilated patients present with diaphragmatic weakness or also know as ventilator-induced diaphragmatic dysfunction (VIDD). The damage to the diaphragm in terms of muscle atrophy has been shown as early as 12 hours after initiation of mechanical ventilation. Recently, a correlation between diaphragmatic atrophy and mortality could be established.

Induction of diaphragmatic contractions via stimulation of the phrenic nerve would be a possible method to prevent or treat VIDD. A possible modality would be the non-invasive electromagnetic stimulation but feasibility has not been established.

In this proof-of-concept trial the primary aim is to show that it is possible to induce a diaphragmatic contraction in critically ill ICU patients via an external electromagnetic stimulation of the phrenic nerve, leading to an inspiration (i) with a sufficient tidal volume (3-6 ml/kg ideal body weight) and (ii) with verifiable muscular diaphragmatic contraction through ultrasound imaging.

Eligibility criteria: Inclusion Criteria:

* Patients between 18 and 60 years old, hospitalized in ICU
* Mechanical ventilation \< 36 h
* Prone to stay ventilated \> 72 h

Exclusion Criteria:

* Known neurological condition affecting motor neuron or muscle (e.g. ALS)
* Known paralysis of the phrenic nerve
* Proven or suspected spinal cord injury that contraindicates weight bearing on the spinal cord
* Conditions that limit diaphragm movement (high intra-abdominal pressure, ascites, obesity)
* Not able to read and understand the national language German
* Patients with Implanted cardiac support systems (pacemaker, implanted defibrillator)
* Patients with implanted medical pumps
* Pregnant patients
* Patients with skin lesions, infections or strictures in throat/neck area
* Patients with metallic implants

Primary outcomes:
measure: Frequency of non-feasible stimulation, due to organisational or patient-specific reasons.
timeFrame: 10 days
measure: Time to find the optimal stimulation point of the N. phrenicus
timeFrame: Study duration (10 days)
measure: Frequency of sufficient Tidal volume generated by electromagentical stimulation of the phrenic nerve (3-6 ml/kg ideal body weight)
timeFrame: Study duration (10 days)
Secondary outcomes:
measure: Variance of Tidal volume generated by electromagentical stimulation of the phrenic nerve
timeFrame: Study duration (10 days)
measure: Correlation between amplitude and duration of sEMG signals during stimulated breathing.
timeFrame: Study duration (10 days)
measure: Transpulmonary pressure during electromagnetical stimulation of the phrenic nerve
timeFrame: Study duration (10 days)
measure: Occlusion pressure during electromagnetical stimulation of the phrenic nerve
timeFrame: Study duration (10 days)
measure: Diaphragm thickening fraction
timeFrame: approx. 28 days (till ICU discharge)
measure: Diaphragm excursion
timeFrame: approx. 28 days (till ICU discharge)
measure: Stimulated tracheal pressure during electromagentical stimulation of the phrenic nerve
timeFrame: Study duration (10 days)
measure: Rapid Shallow Breathing Index (RSBI) record and evaluation.
timeFrame: Study duration (10 days)
measure: Lung compliance during electromagentical stimulation of the phrenic nerve
timeFrame: 10 days
measure: Lung resistance during electromagentical stimulation of the phrenic nerve
timeFrame: 10 days
measure: Maximal inspiratory pressure (MIP) during electromagnetical stimulation of the phrenic nerve.
timeFrame: Study duration (10 days)
measure: Expiratory and Inspiratory Diaphragm Thickness measured by Ultrasound
timeFrame: Study duration (10 days)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Univiversitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Stefan J Schaller, MD
role: PRINCIPAL_INVESTIGATOR
References: