Electromagnetic Stimulation of the Phrenic Nerve in Critically Ill Mechanically Ventilated Patients (STIMIT-II) (STIMIT-II)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Critical Illness; Muscle Weakness; Mechanical Ventilation Complication
• Intervention / Treatment: Device: Non-invasive electromagnetic stimulation

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité - Univiversitätsmedizin Berlin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention, stimulated; Electromagnetic stimulation of the phrenic nerve in critically ill patients.	Device: Non-invasive electromagnetic stimulation; Non-invasive bilateral electromagnetic stimulation of the phrenic nerve
NO_INTERVENTION: Control, not stimulated; Control group, no stimulation of the phrenic nerve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of non-feasible stimulation, due to organisational or patient-specific reasons.	Percentage of non-feasible stimulation out of the total number of stimulations planned according to the investigation protocol.	10 days
Time to find the optimal stimulation point of the N. phrenicus	Time between first successful N. phrenicus stimulation and identification of the optimal stimulation locus in seconds	Study duration (10 days)
Frequency of sufficient Tidal volume generated by electromagentical stimulation of the phrenic nerve (3-6 ml/kg ideal body weight)	Percentage of stimulated breaths above the cut-off Today volume (3-6 ml/kg ideal body weigh) out of the total number of stimulated breaths. Tidal volumes are measured by the mechanical ventilator.	Study duration (10 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variance of Tidal volume generated by electromagentical stimulation of the phrenic nerve	Measurement of variance among the Tidal volumes stimulated during the experimental therapy intervention; Tidal volumes are measured by the mechanical ventilator.	Study duration (10 days)
Correlation between amplitude and duration of sEMG signals during stimulated breathing.	sEMG amplitude and duration are measured by a device (sEMG Amplificator) connected to electrodes applied to the patient's chest during electromagnetic phrenic nerve stimulation.	Study duration (10 days)
Transpulmonary pressure during electromagnetical stimulation of the phrenic nerve	Transpulmonary pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	Study duration (10 days)
Occlusion pressure during electromagnetical stimulation of the phrenic nerve	Occlusion pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	Study duration (10 days)
Diaphragm thickening fraction	Diaphragm thickening fraction measured with ultrasound of the diaphragm.	approx. 28 days (till ICU discharge)
Diaphragm excursion	Diaphragm excursion measured with ultrasound of the diaphragm.	approx. 28 days (till ICU discharge)
Stimulated tracheal pressure during electromagentical stimulation of the phrenic nerve	Stimulated tracheal pressure is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	Study duration (10 days)
Rapid Shallow Breathing Index (RSBI) record and evaluation.	Progression of RSBI during 10 days after subject inclusion, based on the mechanical ventilation parameters (Tidal volume) and the ICU continuous monitoring system (Respiratory Rate).	Study duration (10 days)
Lung compliance during electromagentical stimulation of the phrenic nerve	Lung compliance is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	10 days
Lung resistance during electromagentical stimulation of the phrenic nerve	Lung resistance is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	10 days
Maximal inspiratory pressure (MIP) during electromagnetical stimulation of the phrenic nerve.	MIP is measured by the mechanical ventilator during electromagnetic phrenic nerve stimulation.	Study duration (10 days)
Expiratory and Inspiratory Diaphragm Thickness measured by Ultrasound	Diaphragm Thickness measured by Ultrasound as a baseline parameter for muscle atrophy.	Study duration (10 days)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Stimit AG

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 21, 2022
• Primary Completion (ACTUAL): May 15, 2022
• Study Completion (ACTUAL): May 15, 2022

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (ACTUAL): February 14, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Weaning; VIDD; Muscle Weakness; ICUAW
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Critical Illness; Paresis
• Other Study ID Numbers: STIMIT-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data can be requested on reasonable scientific request.
• IPD Sharing Time Frame: After publication of scientific manuscript.
• IPD Sharing Access Criteria: Deidentified data can be requested on reasonable scientific request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No