Critical illness myopathy and timely electrical muscle stimulation
| ISRCTN | ISRCTN19392591 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN19392591 |
| Protocol serial number | No. 192/2, WE 4386/1-1 |
| Sponsor | Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany) |
| Funders | Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany), German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) (ref: No.192/2, WE 4386/1-1) |
- Submission date
- 10/06/2010
- Registration date
- 17/02/2011
- Last edited
- 04/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Steffen Weber-Carstens
Scientific
Scientific
CC7
Augustenburger Platz 1
Berlin
13353
Germany
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled observer blind clinical trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Critical illness myopathy and timely electrical muscle stimulation: an observer-blinded randomised controlled clinical trial |
| Study objectives | AIM 1 - Hypothesis: Electrical muscle stimulation (EMS) of both lower and upper extremities is associated with increased muscle strength upon emergence from sedation and a lower degree of functional impairment at discharge from intensive care unit (ICU). Test: We will investigate and compare muscle strength (MRC score), functional impairment (functional independence measure) and secondary clinical outcome parameters in both study groups at the end of sedation and at ICU discharge. AIM 2 - Hypothesis: EMS prevents thick filament loss. Test: The extent of thick filament loss will be visualised by histopathological staining and electron microscopy and will be compared between both study groups. Regulation of atrophy gene expression (MURF-I and Atrogin) will be investigated. AIM 3 - Hypothesis: EMS improves systemic insulin sensitivity as well as oxidative metabolism of skeletal muscles in the intervention group. Test: We will investigate key molecules of insulin signalling, MAP-kinase and AMP-kinase in muscle biopsies by Real Time PCR and Western blotting. We will perform RT-PCR studies on the expression pattern of key mitochondrial genes as well as western blots of voltage-dependent anion channels of the outer mitochondrial membrane (VDAC) indicating mitochondrial muscle mass and will compare these parameters between the intervention and control group. AIM 4 - Hypothesis: EMS promotes activation of specific metabolic pathways. Thus, the metabolic adaptations may be critical for the development of CIM in critically ill patients and the metabolic profile may thus serve as a reliable biomarker for disease prediction. Test: Metabolite profiling will be performed on a Pegasus 3 time-of-flight mass spectrometer (Leco) equipped with a Direct Thermal Desorption injector (ATAS GL International) coupled to an HP 5890 gas chromatograph and a dual-arm autosampler with automatic de-vitalisation and liner exchange. Chromatograms will be processed using Leco ChromaTOF software (version 3.25) and peaks with signal to noise ratios >10 and will be exported before using an in-house developed algorithm. Mass spectra will be compared to the in-house mass spectral library according to mass spectral similarity and retention. Principal component analysis (PCA) will be performed on the obtained data to illustrate disparities between intervention and control group on metabolite levels. |
| Ethics approval(s) | Charite - Berlin Medical University (Charite - Universitätsmedizin Berlin) Ethics Committee approved in May 2010 (ref: EA2/041/10) |
| Health condition(s) or problem(s) studied | Intensive Care Unit-acquired weakness (ICUAW)/Critical illness myopathy (CIM) |
| Intervention | Current intervention as of 15/10/2021: Patients allocated to the intervention group will receive EMS treatment of M. quadriceps femoris (M. vastus lateralis and M. rectus femoris), M. tibialis anterior, M. biceps brachii, M. triceps brachii, M. brachioradialis and ventral auxiliary muscles (Th9 - Th11) twice per day. Patients allocated to the control group will receive sham stimulation of respective muscles twice per day by electrode placement without application of electrical current. Within the intervention group, the applied electrical current depends on visible or palpable contracation or patient discomfort (maximum current applied: 70mA, maximum duration of intervention: 28 days). Gender-specific sub-analysis will be performed to investigate potential differences and account for gender bias. _____ Previous intervention: Patients allocated to the intervention group will receive EMS treatment of M. quadriceps femoris (M. vastus lateralis and M. rectus femoris), M. tibialis anterior, M. biceps brachii, M. triceps brachii, M. brachioradialis and ventral auxiliary muscles (Th9 - Th11) twice per day. Patients allocated to the control group will receive sham stimulation of respective muscles twice per day by electrode placement without application of electrical current. Within the intervention group, the applied electrical current depends on visible or palpable contracation or patient discomfort (maximum current applied: 70mA, maximum duration of intervention: 28 days). |
| Intervention type | Other |
| Primary outcome measure(s) |
1. Clinical: muscle strength assessd by MRC score after the end of sedation and functional impairment at ICU discharge as indicated by FIM |
| Key secondary outcome measure(s) |
1. Clinical (assessed during the study enrolment period): |
| Completion date | 30/09/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 80 |
| Total final enrolment | 50 |
| Key inclusion criteria | 1. Adults with a Sequential Organ Failure Assessment (SOFA) score greater than or equal to 9 2. Mechanical ventilation 3. Written informed consent of legal proxy 4. Aged greater than 18 years, either sex |
| Key exclusion criteria | 1. Patients with mechanical ventilation and SOFA less than or equal to 9 for more than 72 hours prior study screening 2. Age less than 18 years 3. No written informed consent by legal proxy 4. Pre-existing neuromuscular disorder 5. Coagulation disorder refractory to therapy 6. Pregnancy 7. Poor prognosis with expected death within the next hours or days |
| Date of first enrolment | 01/10/2010 |
| Date of final enrolment | 30/09/2013 |
Locations
Countries of recruitment
- Germany
Study participating centre
CC7
Berlin
13353
Germany
13353
Germany
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2019 | 12/09/2019 | Yes | No |
| Results article | results | 10/09/2019 | 12/09/2019 | Yes | No |
| Results article | Retrospective analysis | 03/08/2022 | 04/08/2022 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
04/08/2022: Publication reference added.
15/10/2021: The intervention has been updated.
12/09/2019: Publication reference and total final enrolment added.
