Clinical trial NCT06786390: Improved Recovery of Walking in Acquired Muscle Weakness
Official title: Regaining Walking Ability Easier and Better in Critical Illness Polyneuropathy and Myopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critical Illness Myopathy
Critical Illness Polyneuropathy
Keywords: Functional Electrical Stimulation
Acquired Muscle Weakness
Rehabilitation
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
First posted: 2025-01-22
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A double-blind longitudinal RCT will be performed. The subjects enrolled will be divided in two groups on the basis of their diagnosis, CIP/CIM. Subsequently subjects will be randomly assigned either to the experimental group (FES), or to the control group (CON).
Primary purpose: TREATMENT

Brief summary: The aim of Re-Walk-Easy is to evaluate the effects of rehabilitation based on electrical stimulation on the motor performance of critically ill patients. The study will also investigate the pathophysiology of the two forms-the myopathic-predominant and the polyneuropathic-predominant variants-by examining the longitudinal progression of CIP and CIM and determining which form benefits more from electrical stimulation as a rehabilitative approach.

Detailed description: Although rehabilitation is often recommended to patients with Intensive Care Unit Acquired Weakness (ICU-AW) to counteract the induced muscle weakness, systematic reviews failed to determine its efficacy. Neuro Muscular Electrical Stimulation (NMES) is part of clinical practice in ICU-AW however its effects are still under debate. The investigators hypothesize that this uncertainty stems from the lack of distinction between the two forms of the condition-Critical Illness Polyneuropathy (CIP) and Critical Illness Myopathy (CIM)-which have distinct pathological features and disease trajectories. In addition, the investigators hypothesize that motivating patients by requiring voluntary muscle activation during the Electrical Stimulation (i.e. Functional Electrical Stimulation - FES) will enhance rehabilitation.

The study will test the following hypothesis through a longitudinal clinical trial aimed at determining:

1. which form will benefit the most from FES based-rehabilitation,
2. the biomarkers of walking recovery in ICU-AW.

Eligibility criteria: Critical Illness Patient Inclusion Criteria:

* clinical diagnosis of tetra/paraparesis of peripheral origin as disclosed by ENG/EMG examination;
* be independent before the episode of critical illness

Critical Illness Patient Exclusion Criteria:

* history of previous comorbidity for ICU-AW;
* previous known chronic polyneuropathy;
* severe coagulopathy;
* severe disorder of consciousness;
* contraindications to Electrical Stimulation application

Healthy Subjects Exclusion Criteria:

* Prosthetic implants
* musculoskeletal, neurological, cardiovascular and pulmonary disorders that may alter the gait

Primary outcomes:
measure: Medical Research Council - Sum Score (MRC-SS)
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
Secondary outcomes:
measure: Walking velocity on 10 meters walking test
timeFrame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Modified Barthel Index
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Instrumented Six Minute Walk Test
timeFrame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Timed Up and Go Test
timeFrame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Euro Quality of Life-5 -dimension Questionnaire
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Client Satisfaction Questionnaire - CSQ
timeFrame: After 15 rehabilitation sessions (each session is 60 minutes, T2)
measure: Needle Electromyography-based parameters
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Electroneurography (ENG) and Nerve Conduction Studies
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Electroneurography (ENG) and Nerve Conduction Studies
timeFrame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Postural capabilities will be evaluated based on body kinetics
timeFrame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)
measure: Fall diary
timeFrame: From baseline (T0) to 3-month follow-up (T3)
measure: Report of adverse events
timeFrame: From baseline (T0) to post-treatment evaluation, after the 15 rehabilitation sessions (each session is 60 minutes, T2)
Other outcomes:
measure: Gender data
timeFrame: Baseline (T0)
measure: Age data
timeFrame: Baseline (T0)
measure: Scholarity data
timeFrame: Baseline (T0)
Locations:
city: Milano
country: Italy
facility: IRCCS Fondazione Don Carlo Gnocchi Onlus
Study officials:
References:
citation: Van Lancker K, Bretz F, Dukes O. Covariate adjustment in randomized controlled trials: General concepts and practical considerations. Clin Trials. 2024 Aug;21(4):399-411. doi: 10.1177/17407745241251568. Epub 2024 Jun 2.
citation: Dobkin BH. Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions. Neurorehabil Neural Repair. 2009 Mar-Apr;23(3):197-206. doi: 10.1177/1545968309331863.
citation: Gordon T. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans. Neurotherapeutics. 2016 Apr;13(2):295-310. doi: 10.1007/s13311-015-0415-1.
citation: Jonsdottir J, Thorsen R, Aprile I, Galeri S, Spannocchi G, Beghi E, Bianchi E, Montesano A, Ferrarin M. Arm rehabilitation in post stroke subjects: A randomized controlled trial on the efficacy of myoelectrically driven FES applied in a task-oriented approach. PLoS One. 2017 Dec 4;12(12):e0188642. doi: 10.1371/journal.pone.0188642. eCollection 2017.
citation: Perini G, Bertoni R, Thorsen R, Carpinella I, Lencioni T, Ferrarin M, Jonsdottir J. Sequentially applied myoelectrically controlled FES in a task-oriented approach and robotic therapy for the recovery of upper limb in post-stroke patients: A randomized controlled pilot study. Technol Health Care. 2021;29(3):419-429. doi: 10.3233/THC-202371.
citation: Connolly B, O'Neill B, Salisbury L, McDowell K, Blackwood B; Enhanced Recovery After Critical Illness Programme Group. Physical rehabilitation interventions for adult patients with critical illness across the continuum of recovery: an overview of systematic reviews protocol. Syst Rev. 2015 Sep 29;4:130. doi: 10.1186/s13643-015-0119-y.
citation: Mehrholz J, Pohl M, Kugler J, Burridge J, Muckel S, Elsner B. Physical rehabilitation for critical illness myopathy and neuropathy: an abridged version of Cochrane Systematic Review. Eur J Phys Rehabil Med. 2015 Oct;51(5):655-61. Epub 2015 Jul 9.
citation: Liu M, Luo J, Zhou J, Zhu X. Intervention effect of neuromuscular electrical stimulation on ICU acquired weakness: A meta-analysis. Int J Nurs Sci. 2020 Mar 10;7(2):228-237. doi: 10.1016/j.ijnss.2020.03.002. eCollection 2020 Apr 10.
citation: Garcia-Perez-de-Sevilla G, Sanchez-Pinto Pinto B. Effectiveness of physical exercise and neuromuscular electrical stimulation interventions for preventing and treating intensive care unit-acquired weakness: A systematic review of randomized controlled trials. Intensive Crit Care Nurs. 2023 Feb;74:103333. doi: 10.1016/j.iccn.2022.103333. Epub 2022 Oct 22.
citation: Wang W, Xu C, Ma X, Zhang X, Xie P. Intensive Care Unit-Acquired Weakness: A Review of Recent Progress With a Look Toward the Future. Front Med (Lausanne). 2020 Nov 23;7:559789. doi: 10.3389/fmed.2020.559789. eCollection 2020.
citation: Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol. 2011 Oct;10(10):931-41. doi: 10.1016/S1474-4422(11)70178-8.