Improved Recovery of Walking in Acquired Muscle Weakness

Official title

Regaining Walking Ability Easier and Better in Critical Illness Polyneuropathy and Myopathy

Overview

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.

Interventions

• Other Rehabilitation protocol: FES
  Subjects diagnosed with CIP will follow the FES-based rehabilitation protocol
• Other Rehabilitation protocol without FES
  Subjects belonging to the control group will follow the rehabilitation protocol without FES
• Other Rehabilitation protocol: FES
  Subjects diagnosed with CIM will follow the FES-based rehabilitation protocol

Primary outcome measures

• Medical Research Council - Sum Score (MRC-SS) [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]

Secondary outcome measures (12)

• Walking velocity on 10 meters walking test [Time frame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Modified Barthel Index [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Instrumented Six Minute Walk Test [Time frame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Timed Up and Go Test [Time frame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Euro Quality of Life-5 -dimension Questionnaire [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Client Satisfaction Questionnaire - CSQ [Time frame: After 15 rehabilitation sessions (each session is 60 minutes, T2)]
• Needle Electromyography-based parameters [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Electroneurography (ENG) and Nerve Conduction Studies [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Electroneurography (ENG) and Nerve Conduction Studies [Time frame: Baseline (T0), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Postural capabilities will be evaluated based on body kinetics [Time frame: Baseline (T0), 3-week from T0 (T1), after 15 rehabilitation sessions (each session is 60 minutes, T2), 3-month follow-up (T3)]
• Fall diary [Time frame: From baseline (T0) to 3-month follow-up (T3)]
• Report of adverse events [Time frame: From baseline (T0) to post-treatment evaluation, after the 15 rehabilitation sessions (each session is 60 minutes, T2)]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS Fondazione Don Carlo Gnocchi Onlus — Milan

Publications

• 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. PMID 38825841
• 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. PMID 19240197
• 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. PMID 26754579
• 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. PMID 29200424
• 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. PMID 33386831
• 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. PMID 26419458
• 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. PMID 26158919
• 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. PMID 32685621

Identifiers

NCT: NCT06786390 · Re-Walk-Easy-SC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗