MyokinE100 System: Closed Loop Electrical Muscle Stimulation to Mitigate ICU Acquired Weakness in Medical ICU Patients

Lower limb muscle strength will be assessed using the Medical Research Council (MRC) sum score. The MRC sum score grades voluntary muscle contraction for each muscle group from 0 (no contraction) to 5 (normal strength). Six muscle groups in lower limbs will be tested for a total best possible score of 30.

A 1-point increase in MRC score per muscle group in the lower limbs is considered clinically significant.

A single Unanticipated Adverse Device Effect (UADE) in any participant during the study is considered significant.

Upper and lower limb muscle strength will be assessed using the Medical Research Council (MRC) sum score. The MRC sum score scale grades voluntary muscle contraction for each muscle group from 0 (no contraction) to 5 (normal strength). Twelve muscle groups will be tested for a total possible best score of 60.

A 1-point change in MRC sum score is considered clinically significant.

Handgrip muscle strength will be assessed using a handheld dynamometer (HHD) as an indicator of global muscle function. Participants will be considered to have ICU-Acquired Weakness (ICUAW) if the average handgrip strength is below the threshold of 11Kg for men or 7 Kg for woman.

Higher scores in Kg indicate greater global muscle function.

Functional mobility will be assessed using the ICU Mobility Scale (IMS), which ranges from 0 (lying in bed, no active movement) to 10 (walking independently without a gait aid).

Higher scores indicate greater mobility.

Functional exercise capacity will be assessed using the Six-Minute Walk Test (6MWT) which measures the distance a participant can walk on a flat surface in six minutes.

A greater distance walked indicates better functional status.

Functional exercise capacity will be assessed using the 30-Second Sit-to-Stand Test (30 s STS) which measures how many times a person can stand up from and sit down (one repetition) in an armless chair in 30 seconds.

A higher number of repetitions indicates greater functional capacity.

The Rectus Femoris muscle structure will be evaluated using musculoskeletal ultrasound. Measurements will include cross-sectional area, muscle circumference, pennation angle, and echo-intensity.

Higher cross-sectional area, muscle circumference, and pennation angle indicate better muscle structure, while increased echo-intensity suggests worse muscle structure.

Frailty will be assessed using the Clinical Frailty Scale (CFS), which ranges from 1 (very fit) to 7 (severely frail).

Higher scores are worse.

Functional independence will be assessed using the Barthel Index, which measures patient's ability in 10 activities of daily living (feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, chair transfers, mobility on level surfaces, and stairs).

A higher score closer to 100 indicate greater functional independence.

Fatigue will be assessed using the Visual Analog Scale for Fatigue (VAS-F), where participants rate their fatigue on a scale from 0 (no fatigue) to 10 (worst possible fatigue).

Higher scores indicate greater fatigue.

Health-related quality of life will be assessed using the RAND 36-Item Health Survey (SF-36), which evaluates eight domains including physical functioning, role limitations, pain, general health, vitality, social functioning, emotional well-being, and mental health. Scores range from 0 to 100, with higher scores indicating better health status.

Employment status will be assessed during follow-up after hospital discharge using a structured questionnaire. Participants will report their current employment status and whether their ICU stay affected their ability to work.

Return to work is considered best outcome.

The number of days from the initiation of mechanical ventilation to the discontinuation of mechanical ventilation.

A lower number of days is better.

Ventilator-free days will be calculated as 28 minus total number of days on invasive mechanical ventilation during which the participant is alive and not receiving invasive mechanical ventilation.

Participants who die within 28 days will be assigned zero ventilator-free days.

Length of stay will be recorded in three categories: (1) ICU stay, defined as the total number of consecutive days from ICU admission to ICU discharge; (2) ward stay, defined as the number of days spent in a hospital ward after ICU discharge; and (3) total hospital stay, defined as the number of days from hospital admission to hospital discharge.

The shorter the length of stay, the better.

Discharge location will be recorded at the time of hospital discharge using predefined categories: home, home with home health services, inpatient rehabilitation facility, skilled nursing facility, long-term acute care hospital, hospice, or death.

Discharge home is considered the best outcome.

Treatment session tolerance will be assessed using standardized scales.

Tolerance is defined as:

• CPOT less than 7
• NRS less than 8 at the thigh level
• RASS less than +3

Scale ranges:

• CPOT (0 = relaxed, 8 = severe pain/agitation)
• NRS for pain (0 = no pain, 10 = worst pain),
• RASS (-5 = unarousable, +4 = combative)

Electrical interference with cardiac monitoring will be assessed during each electrical muscle stimulation (EMS) session using ECG tracings from standard ICU cardiac monitoring devices. Interference is defined as continuous 60-cycle (60 Hz) artifact for more than 60 seconds that impairs accurate interpretation of cardiac rhythm. ECG data will be captured only during EMS intervention sessions.

Success is defined as 20% or less of ECG samples showing electrical interference as defined above.

"Muscle contraction during electrical muscle stimulation (EMS) sessions will be assessed using the Muscle Contraction Scale, which classifies contraction from Type 1 (no palpable or visible contraction) to Type 5 (palpable and visible contraction with full muscle bulk).

Participants achieved a response if they scored muscle contraction grade 3 or higher.

Quadriceps muscle electrical properties will be measured using Electrical Impedance Myography (EIM). Measurements will include Impedance (Z in ohms), Reactance (X in ohms), and Phase Angle (PA in degrees), which reflect muscle composition.

Lower Phase Angle and Reactance values indicate reduced muscle composition. Higher Impedance values generally indicate reduced muscle health.

C-Terminal Agrin Fragment (CAF) levels will be measured in blood and urine samples collected from enrollment through Day 14. Higher CAF levels may indicate increased neuromuscular junction degradation, while lower levels suggest better preservation of muscle function.