Clinical trial NCT02214823: eStimCycle: Early Rehabilitation in Critical Care
Official title: Functional Electrical Stimulation Assisted Cycling (eStimCycle):A Novel Intervention to Improve Outcomes in the Critically Ill
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intensive Care Unit Acquired Weakness (ICUAW)
Lead sponsor: University of Melbourne
Sponsor class: OTHER
First posted: 2014-08-12
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. ≥18 years,
2. 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
3. predicted ICU length of stay ≥4 days.

Exclusion Criteria:

1. Known primary systemic neuromuscular disease or intracranial process on ICU admission
2. Lower limb amputation/s
3. Unable to perform study physical outcome measures pre morbidly due to condition impairing mobility
4. Assessed by medical staff as not-expected to survive ICU
5. Pregnancy
6. BMI \> 40
7. Presence of external fixator or superficial metal in lower limb
8. Open wounds or skin abrasions at electrode application points
9. Presence of cardiac or diaphragmatic pacemaker or implanted defibrillator with no underlying rhythm, as confirmed by the treating physician
10. Transferred from another ICU after \> 2 days of mechanical ventilation
11. Platelets \< 40 000 and INR \> 1.6 (for muscle biopsy)
12. Lower limb malignancy
13. Pre-existing intellectual disability or cognitive impairment limiting the ability to accurately follow instructions.
14. 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:

1. Cognitive impairment (IQCODE \>3.3) done by proxy after informed consent obtained
2. No fixed home address
3. Score \>= 10 on Alcohol use disorders and identification test (AUDIT)

Primary outcomes:
measure: Muscle mass and cross sectional area
timeFrame: 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
measure: Muscle Strength
timeFrame: 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.
measure: Neuropsychological Battery of Tests
timeFrame: 6 and 12 months post ICU discharge
Secondary outcomes:
measure: Biomarker analyses
timeFrame: Baseline and ICU discharge with an expected average stay of 14 days
measure: Hours of mechanical ventilation, ICU hours and ICU readmission
timeFrame: trial completion
measure: Confusion Assessment Method for ICU (CAM-ICU)
timeFrame: Daily in ICU for an expected average of 14 days
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Hospital discharge and expected stay on average of 4 weeks
measure: Activities of Daily Living and Instrumental Activities of Daily Living
timeFrame: Baseline, 90-day status, 6-month call
measure: Physical function
timeFrame: 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.
measure: Informant Questionnaire on Cognitive Decline in the Elderly, short form (IQCODE-SF)
timeFrame: Baseline
measure: Hospital Anxiety and Depression Scale
timeFrame: 6 and 12 months post recruitment
measure: Impact of Events Scale - Revised (IES-R)
timeFrame: 6 and 12 months post recruitment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
Study officials:
affiliation: University of Melbourne
name: Linda Denehy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Health
name: Susan Berney, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Dale Needham, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Brisbane and Women's Hospital
name: Jennifer Paratz, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parry SM, Berney S, Koopman R, Bryant A, El-Ansary D, Puthucheary Z, Hart N, Warrillow S, Denehy L. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial. BMJ Open. 2012 Sep 13;2(5):e001891. doi: 10.1136/bmjopen-2012-001891. Print 2012.
citation: Parry SM, Berney S, Granger CL, Koopman R, El-Ansary D, Denehy L. Electrical muscle stimulation in the intensive care setting: a systematic review. Crit Care Med. 2013 Oct;41(10):2406-18. doi: 10.1097/CCM.0b013e3182923642.
citation: Parry SM, Berney S, Warrillow S, El-Ansary D, Bryant AL, Hart N, Puthucheary Z, Koopman R, Denehy L. Functional electrical stimulation with cycling in the critically ill: a pilot case-matched control study. J Crit Care. 2014 Aug;29(4):695.e1-7. doi: 10.1016/j.jcrc.2014.03.017. Epub 2014 Mar 26.
citation: Berney S, Hopkins RO, Rose JW, Koopman R, Puthucheary Z, Pastva A, Gordon I, Colantuoni E, Parry SM, Needham DM, Denehy L. Functional electrical stimulation in-bed cycle ergometry in mechanically ventilated patients: a multicentre randomised controlled trial. Thorax. 2021 Jul;76(7):656-663. doi: 10.1136/thoraxjnl-2020-215093. Epub 2020 Dec 15.
citation: Parry SM, Denehy L, Beach LJ, Berney S, Williamson HC, Granger CL. Functional outcomes in ICU - what should we be using? - an observational study. Crit Care. 2015 Mar 29;19(1):127. doi: 10.1186/s13054-015-0829-5.