Skeletal muscle metabolism and Critical Illness Myopathy (CIM) during early course of systemic inflammation
| ISRCTN | ISRCTN77569430 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77569430 |
| Secondary identifying numbers | No. 192/0, WE 4386/1-1 |
- Submission date
- 21/10/2007
- Registration date
- 13/02/2008
- Last edited
- 04/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Signs and Symptoms
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
Augustenburger Platz 1
Berlin
13353
Germany
| Phone | +49 30 450651055 |
|---|---|
| steffen.weber-carstens@charite.de |
Study information
| Study design | Phase 1: Observational. Phase 2: Interventional (randomly assigned side of intervention) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Skeletal muscle metabolism and Critical Illness Myopathy (CIM) during early course of systemic inflammation |
| Study objectives | Amended 15/11/10: Hypothesis 2: Electrical muscle stimulation has been demonstrated to improve the muscle insulin sensitivity and might thereby prevent the development of CIM Test: To investigate the safety and efficacy of electrical muscle stimulation in critically ill patients during early systemic inflammation or sepsis as a potential therapeutic approach to prevent CIM Hypothesis 2 will be tested by an intraindividual interventional study (Phase 2). Initial information at time of registration: Hypothesis 1: Impaired insulin sensitivity may be involved in the development of CIM secondary to systemic inflammation or sepsis and may lead to skeletal muscle protein breakdown Test 1: To identify metabolic and/or inflammatory parameters in patients, which allow identification of individuals who develop CIM during early course of systemic inflammation and/or sepsis Test 2: To investigate histomorphological changes during early course of systemic inflammation or sepsis in patients who develop CIM Hypothesis 1 will be tested by an observational pilot study (Phase 1). Hypothesis 2: Low frequency electrical muscle stimulation has been demonstrated to improve the muscle insulin sensitivity and might thereby prevent the development of CIM Test: To investigate the safety and efficacy of low frequency electrical muscle stimulation in critically ill patients during early systemic inflammation or sepsis as a potential therapeutic approach to prevent CIM Hypothesis 2 will be tested by an interventional study (Phase 2). Please note that as of 15/11/10 this record has been updated to include amendments to the protocol relating to the replacement of the parallel-group intervention with an intraindivdual intervention. All updates may be found in the relevant field with the above update date. |
| Ethics approval(s) | Approved by the Charite - Berlin Medical University (Charite - Universitätsmedizin Berlin) Ethics Committee on 8th of June 2006 (ref: EA2/061/06). Amendment to the protocol approved on the 10th of December 2009. |
| Health condition(s) or problem(s) studied | Critical illness myopathy (CIM) |
| Intervention | Current intervention as of 15/10/2021: The following will be carried out in the Phase 1 observational pilot study: 1. Severity of illness, organ failure: 1.1. Sequential Organ Failure Assessment (SOFA) score, assessed daily until discharge from ICU or for 28 days 1.2. Acute Physiology and Chronic Health Evaluation (APACHE) II, assessed daily until discharge from ICU or for 28 days 1.3. Acute Physiology Score (SAPS) -II, III, assessed daily until discharge from ICU or for 28 days 2. Nursing workload: Therapeutic Interventions Scoring System-28 (TISS-28), assessed daily until discharge from ICU or for 28 days 3. Clinical neurological assessment: 3.1. Richmond Agitation Sedation Scale (RASS), assessed daily until discharge from ICU or for 28 days 3.2. Delirium Detection Score (DDS), assessed daily until discharge from ICU or for 28 days 3.3. The Medical Research Council (MRC) score (measures motor strength), assessed daily until discharge from ICU or for 28 days 3.4. Daily questionnaire of 5 standardized questions to assess comprehension 4. Clinical sepsis parameters: 4.1. Predisposition, Infection, Host response, Organ dysfunction (PIRO), assessed daily (day 1 - 14) 4.2. Hemodynamics, assessed daily (day 1 - 14) 5. Nutritional support and insulin/glucose adjustments: 5.1. Feeding protocol, assessed daily (day 1 - 14) 5.2. Insulin protocol, assessed daily (day 1 - 14) 5.3. Glucose monitoring, assessed daily (day 1 - 14) 6. Medication from charts, filled by the nurse daily (day 1 - 14) 7. Blood sample: 7.1. Nutritional markers (insulin, insulin like growth factors and binding proteins [IgF's, IGFBP's and TGF-beta]), assessed daily (day 1 - 14) 7.2. Inflammatory markers (flow cytometry), assessed daily (day 1 - 14) 8. Electrophysiology (ElectroMyoGraphy [EMG]/ElectroNystagmoGraphy ENG, Direct Muscle Stimulation [DMS]), carried out on Day 4 and 12, and at day of discharge from ICU 9. Hyperinsulinemic-euglycemic clamp: 9.1. Microdialysis, carried out on Day 4 and Day 12 9.2. Spectrophotometry, carried out on Day 4 and Day 12 9.3. Indirect calorimetry, carried out on Day 4 and Day 12 10. Muscle biopsies (Surgical biopsy), carried out on Day 4 and Day 12 11. Daily bioimpedance measurements Phase 2 interventional study: Phase 2 intraindividual intervention study: Side of unilateral electrical muscle stimulation (EMS) will be randomly assigned and treated with twice daily EMS of tibial anterior and vastus lateral muscles. Control group will receive usual care only. Gender-specific sub-analysis will be performed to investigate potential differences in skeletal muscle metabolism and CIM and account for gender bias. _____ Previous intervention: Amended 15/11/10: Phase 2 intraindividual intervention study: Side of unilateral electrical muscle stimulation (EMS) will be randomly assigned and treated with twice daily EMS of tibial anterior and vastus lateral muscles. Initial information at time of registration: The following will be carried out in the Phase 1 observational pilot study: 1. Severity of illness, organ failure: 1.1. Sequential Organ Failure Assessment (SOFA) score, assessed daily until discharge from ICU or for 28 days 1.2. Acute Physiology and Chronic Health Evaluation (APACHE) II, assessed daily until discharge from ICU or for 28 days 1.3. Acute Physiology Score (SAPS) -II, III, assessed daily until discharge from ICU or for 28 days 2. Nursing workload: Therapeutic Interventions Scoring System-28 (TISS-28), assessed daily until discharge from ICU or for 28 days 3. Clinical neurological assessment: 3.1. Richmond Agitation Sedation Scale (RASS), assessed daily until discharge from ICU or for 28 days 3.2. Delirium Detection Score (DDS), assessed daily until discharge from ICU or for 28 days 3.3. The Medical Research Council (MRC) score (measures motor strength), assessed daily until discharge from ICU or for 28 days 3.4. Daily questionnaire of 5 standardized questions to assess comprehension 4. Clinical sepsis parameters: 4.1. Predisposition, Infection, Host response, Organ dysfunction (PIRO), assessed daily (day 1 - 14) 4.2. Hemodynamics, assessed daily (day 1 - 14) 5. Nutritional support and insulin/glucose adjustments: 5.1. Feeding protocol, assessed daily (day 1 - 14) 5.2. Insulin protocol, assessed daily (day 1 - 14) 5.3. Glucose monitoring, assessed daily (day 1 - 14) 6. Medication from charts, filled by the nurse daily (day 1 - 14) 7. Blood sample: 7.1. Nutritional markers (insulin, insulin like growth factors and binding proteins [IgF's, IGFBP's and TGF-beta]), assessed daily (day 1 - 14) 7.2. Inflammatory markers (flow cytometry), assessed daily (day 1 - 14) 8. Electrophysiology (ElectroMyoGraphy [EMG]/ElectroNystagmoGraphy ENG, Direct Muscle Stimulation [DMS]), carried out on Day 4 and 12, and at day of discharge from ICU 9. Hyperinsulinemic-euglycemic clamp: 9.1. Microdialysis, carried out on Day 4 and Day 12 9.2. Spectrophotometry, carried out on Day 4 and Day 12 9.3. Indirect calorimetry, carried out on Day 4 and Day 12 10. Muscle biopsies (Surgical biopsy), carried out on Day 4 and Day 12 11. Daily bioimpedance measurements Phase 2 interventional study: After an observational pilot phase of the study, patients will be randomized into two groups. Those who are allocated to the intervention group will receive Electrical Muscle Stimulation (EMS) daily (day 1 - 14). Control group will receive usual care only. Scientific contact/ Co-investigator: Dr Joachim Spranger Charité - Berlin Medical University Department of Endocrinology Diabetes and Nutritional Medicine Hindenburgdamm 30 12007 Berlin Germany Email: joachim.spranger@charite.de |
| Intervention type | Other |
| Primary outcome measure | Primary outcome measures for both observational and interventional studies: Insulin sensitivity: 1. Studies of the insulin receptor pathways such as IRS, PI3K, AKT and Glut4 will be performed 2. Glucose uptake as well as Insulin-Receptor kinase and PI3Kinase-activities will be determined 3. Hyperinsulinemic-euglycemic clamp will be performed Histopathology on muscle biopsies: Type II myosin loss will be investigated |
| Secondary outcome measures | Secondary outcome measure for both observational and interventional studies: Electrophysiology: Measurement of membrane excitability |
| Overall study start date | 01/10/2007 |
| Completion date | 30/09/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 80 |
| Key inclusion criteria | Critically ill patients with the Sequential Organ Failure Assessment (SOFA) score greater than or equal to 8 on 3 of the 5 successive days within 7 days after admission to ICU. |
| Key exclusion criteria | 1. Patients under age of 18 2. Missing written informed consent from a legal proxy 3. Pretreatment in ICU >7 days |
| Date of first enrolment | 01/10/2007 |
| Date of final enrolment | 30/09/2010 |
Locations
Countries of recruitment
- Germany
Study participating centre
Augustenburger Platz 1
Berlin
13353
Germany
13353
Germany
Sponsor information
Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
University/education
University/education
c/o Prof Friedrich Luft
European Clinical Research Center
Charite Campus Buch
Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Berlin-Buch
Robert-Rössle-Str. 10
Berlin
13092
Germany
"ROR" |
https://ror.org/001w7jn25 |
|---|
Funders
Funder type
Research organisation
Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
No information available
German Research Foundation (DFG) (ref: No.192/1, WE 4386/1-1)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 | 15/02/2013 | Yes | No | |
| Results article | results | 20/03/2014 | Yes | No | |
| Results article | results | 01/04/2014 | Yes | No | |
| Results article | results | 29/09/2014 | Yes | No | |
| Results article | 01/02/2020 | 01/06/2021 | Yes | No | |
| Results article | Retrospective analysis | 03/08/2022 | 04/08/2022 | Yes | No |
Editorial Notes
04/08/2022: Publication reference added.
15/10/2021: The intervention has been updated.
01/06/2021: Publication reference added.
