Neuromuscular Electrical Stimulation in Patients With COVID19 Associated Pneumonia

• ClinicalTrials.gov Identifier: NCT04382729
• Recruitment Status: Recruiting
• First Posted: May 11, 2020
• Last Update Posted: May 11, 2020
• Sponsor: University of Turin, Italy
• Collaborator: San Luigi Gonzaga Hospital
• Information provided by (Responsible Party): Marco Alessandro Minetto, University of Turin, Italy

Tracking Information

• First Submitted Date: May 8, 2020
• First Posted Date: May 11, 2020
• Last Update Posted Date: May 11, 2020
• Actual Study Start Date: April 17, 2020
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 8, 2020)

Short Physical Performance Battery (SPPB) Score [ Time Frame: 1 week after the intervention ]

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: May 8, 2020)

• Functional Independence Measure (FIM) Scale Score [ Time Frame: Before and 1 week after the intervention ]
  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)
• Fatigue Severity Scale Score [ Time Frame: Before and 1 week after the intervention ]
  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
• Muscle Strength [ Time Frame: Before and 1 week after the intervention ]
  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.
• Two Step Test Length [ Time Frame: 1 week after the intervention ]
  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).
• Six Minutes Walking Test Distance [ Time Frame: 1 week after the intervention ]
  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.
• Muscle Thickness [ Time Frame: Before and 1 week after the intervention ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neuromuscular Electrical Stimulation in Patients With COVID19 Associated Pneumonia
• Official Title: Effects of Neuromuscular Electrical Stimulation Therapy on Physical Function in Patients With COVID-19 Associated Pneumonia: Study Protocol of a Randomized Controlled Trial
• Brief Summary: 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Supportive Care
• Condition: COVID-19 Pneumonia

Intervention

• 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.
• 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.

Study Arms

• Experimental: NMES Group
  Intervention: Other: Neuromuscular Electrical Stimulation
• Active Comparator: Control Group
  Intervention: Other: Physical Therapy Exercise

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 8, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2020
• Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marco Alessandro Minetto, MD, PhD; +39 011 6705472‬; marco.minetto@unito.it

Contact: Chiara Busso, MD; +39 011 6705472‬; chiara.busso@unito.it

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04382729
• Other Study ID Numbers: ESC270320
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Marco Alessandro Minetto, University of Turin, Italy
• Study Sponsor: University of Turin, Italy
• Collaborators: San Luigi Gonzaga Hospital

Investigators

• Principal Investigator: Marco Alessandro Minetto, MD, PhD; University of Turin, Italy

• PRS Account: University of Turin, Italy
• Verification Date: May 2020