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

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

Study designPhase 1: Observational. Phase 2: Interventional (randomly assigned side of intervention)
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typePrevention
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleSkeletal muscle metabolism and Critical Illness Myopathy (CIM) during early course of systemic inflammation
Study hypothesisAmended 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.
ConditionCritical illness myopathy (CIM)
InterventionCurrent 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 typeOther
Primary outcome measurePrimary 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 measuresSecondary outcome measure for both observational and interventional studies:

Electrophysiology: Measurement of membrane excitability
Overall study start date01/10/2007
Overall study end date30/09/2010

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants80
Participant inclusion criteriaCritically 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 exclusion criteria1. Patients under age of 18
2. Missing written informed consent from a legal proxy
3. Pretreatment in ICU >7 days
Recruitment start date01/10/2007
Recruitment end date30/09/2010

Locations

Countries of recruitment

  • Germany

Study participating centre

Augustenburger Platz 1
Berlin
13353
Germany

Sponsor information

Charité - University Medicine Berlin (Charité - Universitätsmedizin Berlin) (Germany)
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 logo "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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot 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.