Skeletal muscle metabolism and Critical Illness Myopathy (CIM) during early course of systemic inflammation

ISRCTN	ISRCTN77569430
DOI	https://doi.org/10.1186/ISRCTN77569430
Protocol serial number	No. 192/0, WE 4386/1-1
Sponsor	Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
Funders	Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany), German Research Foundation (DFG) (ref: No.192/1, 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

Augustenburger Platz 1
Berlin
13353
Germany

Phone	+49 30 450651055
Email	steffen.weber-carstens@charite.de

Study information

Primary study design	Interventional
Study design	Phase 1: Observational. Phase 2: Interventional (randomly assigned side of intervention)
Secondary study design	Randomised controlled trial
Study type	Participant 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(s)	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
Key secondary outcome measure(s)	Secondary outcome measure for both observational and interventional studies: Electrophysiology: Measurement of membrane excitability
Completion date	30/09/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	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

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	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
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.
01/06/2021: Publication reference added.