Contact information
Type
Scientific
Primary contact
Dr Steffen Weber-Carstens
ORCID ID
Contact details
Augustenburger Platz 1
Berlin
13353
Germany
+49 30 450651055
steffen.weber-carstens@charite.de
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
No. 192/0, WE 4386/1-1
Study information
Scientific title
Skeletal muscle metabolism and Critical Illness Myopathy (CIM) during early course of systemic inflammation
Acronym
Study hypothesis
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
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.
Study design
Phase 1: Observational. Phase 2: Interventional (randomly assigned side of intervention)
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Critical Illness Myopathy (CIM)
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
Phase
Not Applicable
Drug names
Primary outcome measures
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 trial start date
01/10/2007
Overall trial end date
30/09/2010
Reason abandoned
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
80
Participant exclusion criteria
1. Patients under age of 18
2. Missing written informed consent from a legal proxy
3. Pretreatment in ICU >7 days
Recruitment start date
01/10/2007
Recruitment end date
30/09/2010
Locations
Countries of recruitment
Germany
Trial participating centre
Augustenburger Platz 1
Berlin
13353
Germany
Sponsor information
Organisation
Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
Sponsor details
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
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
German Research Foundation (DFG) (ref: No.192/1, WE 4386/1-1)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23239154
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24651840
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24531339
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25263070
Publication citations
-
Results
Weber-Carstens S, Schneider J, Wollersheim T, Assmann A, Bierbrauer J, Marg A, Al Hasani H, Chadt A, Wenzel K, Koch S, Fielitz J, Kleber C, Faust K, Mai K, Spies CD, Luft FC, Boschmann M, Spranger J, Spuler S, Critical illness myopathy and GLUT4: significance of insulin and muscle contraction., Am. J. Respir. Crit. Care Med., 2013, 187, 4, 387-396, doi: 10.1164/rccm.201209-1649OC.
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Results
Langhans C, Weber-Carstens S, Schmidt F, Hamati J, Kny M, Zhu X, Wollersheim T, Koch S, Krebs M, Schulz H, Lodka D, Saar K, Labeit S, Spies C, Hubner N, Spranger J, Spuler S, Boschmann M, Dittmar G, Butler-Browne G, Mouly V, Fielitz J, Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy, PLoS One, 2014, 9, 3, doi: 10.1371/journal.pone.0092048.
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Results
Wollersheim T, Woehlecke J, Krebs M, Hamati J, Lodka D, Luther-Schroeder A, Langhans C, Haas K, Radtke T, Kleber C, Spies C, Labeit S, Schuelke M, Spuler S, Spranger J, Weber-Carstens S, Fielitz J, Dynamics of myosin degradation in intensive care unit-acquired weakness during severe critical illness, Intensive Care Med, 2014, 40, 4, 528-538, doi: 10.1007/s00134-014-3224-9.
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Results
Schmidt F, Kny M, Zhu X, Wollersheim T, Persicke K, Langhans C, Lodka D, Kleber C, Weber-Carstens S, Fielitz J, The E3 ubiquitin ligase TRIM62 and inflammation-induced skeletal muscle atrophy, Crit Care, 2014, 18, 5, 545, doi: 10.1186/s13054-014-0545-6.