Condition category
Signs and Symptoms
Date applied
21/10/2007
Date assigned
13/02/2008
Last edited
10/11/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

Additional files

Editorial Notes