Neuromuscular Electrical Stimulation in Patients With COVID19 Associated Pneumonia

Effects of Neuromuscular Electrical Stimulation Therapy on Physical Function in Patients With COVID-19 Associated Pneumonia: Study Protocol of a Randomized Controlled Trial

Neuromuscular electrical stimulation (NMES) has been considered as a promising approach for the early rehabilitation of patients in and/or after the intensive care unit (ICU). Aim of this study is to evaluate the NMES effect on physical function of COVID-19 patients.

Study Overview

• Status: Unknown
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Other: Neuromuscular Electrical Stimulation; Other: Physical Therapy Exercise

Detailed Description

This prospective, randomized, controlled, parallel-group, single-blind trial will include 80 patients who had undergone mechanical or non-invasive ventilation following pneumonia-induced respiratory failure. Patients are randomized to a control group (routine physical therapy for 3 weeks) or a NMES group (routine physical therapy plus NMES of quadriceps and gastrocnemius muscles for 3 weeks). The primary outcome is physical performance assessed through the Short Physical Performance Battery (SPPB). Secondary outcomes include independence level, perceived fatigue, muscle strength, rectus femoris thickness, and walking performance. The SPBB and walking performance will be assessed once (after the 3-week intervention period), while all other outcomes will be assessed twice (before and after the intervention).

NMES is a simple and non-invasive technique for muscle strengthening that is usually well tolerated, does not produce adverse effects, requires no or little cooperation from patients and is quite inexpensive. Therefore, proving the effectiveness of NMES therapy for physical and muscle function in COVID-19 patients could support its systematic incorporation in post-ICU rehabilitation protocols of patients presenting with post-intensive care syndrome.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marco Alessandro Minetto, MD, PhD; Phone Number: +39 011 6705472‬; Email: marco.minetto@unito.it
• Study Contact Backup: Name: Chiara Busso, MD; Phone Number: +39 011 6705472‬; Email: chiara.busso@unito.it

Study Locations

• Italy
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • San Luigi Gonzaga Hospital
      • Contact: Federica Gamna, MD; Phone Number: +39 0119026994; Email: f.gamna@sanluigi.piemonte.it
      • Contact: Sabrina Dal Fior, MD; Phone Number: +39 0119026994; Email: s.dalfior@sanluigi.piemonte.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age above 18 years
• respiratory (PaO2/FiO2 ratio > 180 mmHg) and hemodynamic stability for at least two days after withdrawal of mechanical ventilation and neuromuscular blocking agents

Exclusion Criteria:

• pregnancy
• known or suspected malignancy in the lower limbs
• body mass index equal or greater than 35 kg/m2
• conditions preventing NMES treatment (e.g., deep vein thrombosis, skin lesions, rhabdomyolysis)
• conditions preventing the outcome assessment (e.g., amputation or inability to transfer independently from bed to chair before hospital admission)
• presence of an implanted cardiac pacemaker or defibrillator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group	Other: Physical Therapy Exercise; The control group is subjected to a protocol of physical therapy exercises, applied once a day for 30 minutes (5 days per week for 3 weeks) by the staff physical therapists. It starts with global passive range of motion exercises, followed by active and resistive exercises (including controlled breathing exercises and respiratory muscle training), transfer to the edge of the bed or to a chair, standing and walking.
Experimental: NMES Group	Other: Neuromuscular Electrical Stimulation; The intervention group, in addition to the daily routine physical therapy, receives NMES for 15 days (5 days per week for 3 weeks). NMES is applied bilaterally using an electrical stimulator with pairs of electrodes placed transversally on the quadriceps muscles and on the gastrocnemius muscles. The stimulation protocol consists in the application of symmetrical biphasic rectangular pulses with a frequency of 30 Hz (pulse duration: 400 µs). Stimulation intensity is adjusted daily by the physical therapist to elicit a visible twitch in each muscle. The total duration of the NMES session is 30 min for the first week and 45 min for the second and third week. Stimulation (on) time is 5 s and relaxation (off) time is 15 s, thus eliciting a total of 90 evoked contractions per day during the first week and 135 contractions per day during the second and third week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short Physical Performance Battery (SPPB) Score	The SPPB score is a composite measure assessing standing balance (ability to stand for up to 10 seconds with feet positioned in three ways: together side-by-side, semi-tandem and tandem), walking speed (time to complete a 4-m walk), and sit-to- stand performance (time to rise from a chair five times). Each task is scored out of 4 points, with the scores from the three tests summed up to give a total, with a maximum of 12 points and a minimum of 0.	1 week after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Independence Measure (FIM) Scale Score	The FIM is an 18-item, clinician-reported scale that assesses function in six areas including self-care, continence, mobility, transfers, communication, and cognition. Each of the 18 items is graded on a scale of 1-7 based on level of independence in that item (1 = total assistance required, 7 = complete independence)	Before and 1 week after the intervention
Fatigue Severity Scale Score	The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle	Before and 1 week after the intervention
Muscle Strength	Handgrip strength is assessed for both sides using a handheld device. Patients are instructed to perform a maximal voluntary isometric contraction by contracting their muscles as forcefully as possible for 4-5 s. The test is repeated three times for each side and the highest value is retained. Lower limb strength is assessed as the sum of knee extension and plantar flexion strength of both sides. Muscle strength is rated using the Medical Research Council (MRC) scale that ranges from 0 (no muscle contraction) to 5 (normal resistance), for a maximum score of 20 points.	Before and 1 week after the intervention
Two Step Test Length	Subjects are required to step out with the dominant leg maximally, then to step out with the other leg maximally, and then to draw and match the first leg to the second leg while maintaining body stability with either supporting leg. The distance between the start line and the tiptoe of the second step foot is measured as the double step length (sum of the first and second steps).	1 week after the intervention
Six Minutes Walking Test Distance	The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.	1 week after the intervention
Muscle Thickness	Ultrasound-derived muscle thickness is measured as the distance between the superficial and deep aponeuroses of the rectus femoris muscle (that is measured half-way along the line from the anterior-superior iliac spine to the superior border of the patella). Three consecutive static scans of the rectus femoris of both thighs are acquired in the transverse plane and the mean of six measurements (three measurements per side) is considered.	Before and 1 week after the intervention

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Collaborators: San Luigi Gonzaga Hospital
• Investigators: Principal Investigator: Marco Alessandro Minetto, MD, PhD, University of Turin, Italy

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (Actual): May 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 11, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Fatigue; COVID-19; Neuromuscular Electrical Stimulation; Post-Intensive Care Syndrome; Short Physical Performance Battery; Muscle Thickness; Quadriceps Muscle
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: ESC270320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

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