eStimCycle: Early Rehabilitation in Critical Care

Study Overview
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Brief Summary
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Project Summary: Patients who have a length of stay four or more days in ICU and requiring mechanical ventilation assistance to breathe for more than 48 hours will be invited to participate. Participants will be randomised to either receive Functional Electrical Stimulation (eStimCycle) assisted cycling or standard care. As cycling in bed has previously been shown to improve physical function, patients who receive cycling as a treatment will have one leg that cycles and the other leg that cycles with assistance of electrical stimulation as we want to establish the effectiveness of the addition of electrical stimulation of muscle. Muscle bulk, strength and physical function outcome measures will be measured at baseline, weekly in ICU, ICU discharge and hospital discharge. Cognitive function will also be measured at hospital discharge, 6- and 12-month follow-up. A small group of patients in this study will be invited to provide samples of blood, urine and muscle at ICU admission and discharge to try and determine what happens to muscle in patients who are critically ill. Significance of the Project: This is an important study because the development of ICU-acquired weakness (ICU-AW) can result in long term limitations in physical function. Early treatment to maintain strong muscles during an intensive care stay may help speed up recovery and enhance participation in other rehabilitation treatments and improve functional activities and cognition. These are important objectives for both patients and their families. In addition understanding why the muscles become so weak so quickly in patients in ICU will help to develop treatments that may help to maintain muscle strength. Study Hypotheses: Hypothesis 1: eStimCycle versus usual care rehabilitation will improve muscle strength at hospital discharge. Hypothesis 2: eStimCycle versus usual care rehabilitation will improve cognitive function at 6 month follow up. Hypothesis 3: Patients receiving eStimCycle will have improved activity of anabolic signalling pathways and less atrophy of skeletal muscle fibre size compared with usual care rehabilitation.

Official Title
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Functional Electrical Stimulation Assisted Cycling (eStimCycle):A Novel Intervention to Improve Outcomes in the Critically Ill

Conditions
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Intensive Care Unit Acquired Weakness (ICUAW)

Intervention / Treatment
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* Device: FES-Cycling
* Other: Standard Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years, expected mechanical ventilation or ECMO >48 h with evidence of systemic inflammation as defined by American College of Chest Physicians (ACCP) Consensus Conference Criteria and predicted ICU length of stay ≥4 days. Exclusion Criteria: Known primary systemic neuromuscular disease or intracranial process on ICU admission Lower limb amputation/s Unable to perform study physical outcome measures pre morbidly due to condition impairing mobility Assessed by medical staff as not-expected to survive ICU Pregnancy BMI > 40 Presence of external fixator or superficial metal in lower limb Open wounds or skin abrasions at electrode application points Presence of cardiac or diaphragmatic pacemaker or implanted defibrillator with no underlying rhythm, as confirmed by the treating physician Transferred from another ICU after > 2 days of mechanical ventilation Platelets < 40 000 and INR > 1.6 (for muscle biopsy) Lower limb malignancy Pre-existing intellectual disability or cognitive impairment limiting the ability to accurately follow instructions. Non-English speaking background restricting the individuals ability to accurately and consistently follow instructions. Exclusion criteria for the 6 and 12 month cognitive testing follow-up portion of the study: Cognitive impairment (IQCODE >3.3) done by proxy after informed consent obtained No fixed home address Score >= 10 on Alcohol use disorders and identification test (AUDIT)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FES-Cycling<br>Timeframe: Within 72 hours of ICU admission. Program: Standard care physiotherapy AND up to one hour of supine cycling daily using a cycle ergometer (RT300 supine model Restorative Therapies, Ltd or Letto 300.) attached to a six channel stimulator (SAGE) and 2 additional RT50 wireless stimulator channels. One leg will undergo cycling alone without the electrodes turned on (sham) and the other leg will undergo cycling and muscle stimulation. Electrodes will be placed on all major lower limb muscles. Intervention will be provided individually and supervised by a physiotherapist in ICU only. Duration /Intensity: Up to 1 hour at least 5 times a week for 28 days or ICU discharge, if 20 sessions have not occurred at this time, intervention will continue until this is achieved. Intensity of muscle stimulation will be delivered at a level able to cause visible muscle contractions, confirmed by palpation. A subgroup of 10 individuals will be involved in biomarker analyses. | Device: FES-Cycling<br> <br> * Other names: Cycle ergometer (RT300 supine model Restorative Therapies, Ltd or Letto 300.), six channel SAGE stimulator and two RT50 wireless stimulator channels.;Other: Standard Care<br>* standard care physiotherapy including respiratory and rehabilitation with mobilisation activities such as sitting out of bed, marching on the spot, and mobility training.<br>|
| Active Comparator: Standard Care<br>Both groups will receive usual medical and nursing care in the ICU and ward. Both groups (control and intervention) will receive standard care physiotherapy including respiratory and rehabilitation with mobilisation activities such as sitting out of bed, marching on the spot, and mobility training. A subgroup of 10 individuals will be involved in biomarker analyses. This will involve collection of muscle biopsy, blood and urine analyses at baseline and ICU discharge. | Other: Standard Care<br>* standard care physiotherapy including respiratory and rehabilitation with mobilisation activities such as sitting out of bed, marching on the spot, and mobility training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle mass and cross sectional area | Bioimpedance Spectroscopy will be used to evaluate changes in muscle mass. Ultrasonography of the quadriceps will assess changes in muscle thickness and cross sectional area | Baseline, weekly in ICU for an average 2 weeks and at CU discharge (on average 14 days) with participants beng followed for the duration of hospital stay, an expected average of 4 weeks | 
| Muscle Strength | This will be assessed using the Medical Research Council Scale for identifying muscle weakness in ICU and also hand-held dynamometry for grip strength and isometric quadriceps strength | Baseline, weekly in ICU for an average 2 weeks and at ICU discharge (on average 14 dats) with participants beng followed for the duration of hospital stay on average of 4 weeks. Hand-held dynamometry will also be assessed at 6 and 12 months. | 
| Neuropsychological Battery of Tests | Including the following tests: Hayling Sentence Completion, Weschler Adult Intelligence Scale (Digit Span and Similarities), Weschler Memory III (Logical Memory 1 and 2) and Cognistat (Judgment and Orientation), and Controlled Oral Word Association | 6 and 12 months post ICU discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker analyses | Muscle biopsy, 24 hour urine collection and blood analyses in subgroup of n=20 from main pilot randomised controlled trial. | Baseline and ICU discharge with an expected average stay of 14 days | 
| Hours of mechanical ventilation, ICU hours and ICU readmission | This will be collected from medical records data. This will all be reported at the completion of the trial | trial completion | 
| Confusion Assessment Method for ICU (CAM-ICU) | The CAM-ICU is a tool for screening for delirium in critically ill patients. | Daily in ICU for an expected average of 14 days | 
| Montreal Cognitive Assessment (MoCA) | A screening tool for cognitive impairment | Hospital discharge and expected stay on average of 4 weeks | 
| Activities of Daily Living and Instrumental Activities of Daily Living | Two short and simple questionnaires assessing activities of daily living. | Baseline, 90-day status, 6-month call | 
| Physical function | The physical function in ICU test (PFIT), functional status score in the ICU (FSS-ICU), short physical performance battery (SPPB) and six minute walk test (6MWT). | Baseline and then weekly until ICU discharge an expected stay on average of 14 days. SPPB and 6MWT will also be measured at hospital discharge with an average length of stay of 4 weeks. 6MWT will be assessed and 6 and 12 months. | 
| Informant Questionnaire on Cognitive Decline in the Elderly, short form (IQCODE-SF) | The IQCODE-SF for cognitive dysfunction will be completed at baseline by the proxy after obtaining informed consent. | Baseline | 
| Hospital Anxiety and Depression Scale | A scale used to detect the states of anxiety and depression | 6 and 12 months post recruitment | 
| Impact of Events Scale - Revised (IES-R) | IES-R is an instrument to measure the subjective response to a specific traumatic event, especially in the response sets of intrusion (intrusive thoughts, nightmares, intrusive feelings and imagery, dissociative-like re-experiencing), avoidance (numbing of responsiveness, avoidance of feelings, situations, and ideas), and hyperarousal (anger, irritability, hypervigilance, difficulty concentrating, heightened startle), as well as a total subjective stress IES-R score. | 6 and 12 months post recruitment |