Condition category
Musculoskeletal Diseases
Date applied
10/06/2010
Date assigned
17/02/2011
Last edited
17/02/2011
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

CC7
Augustenburger Platz 1
Berlin
13353
Germany

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

No. 192/2, WE 4386/1-1

Study information

Scientific title

Critical illness myopathy and timely electrical muscle stimulation: an observer-blinded randomised controlled clinical trial

Acronym

Study hypothesis

AIM 1 - Hypothesis: Electrical muscle stimulation (EMS) of both lower and upper extremities is associated with increased muscle strength upon emergence from sedation and a lower degree of functional impairment at discharge from intensive care unit (ICU).
Test: We will investigate and compare muscle strength (MRC score), functional impairment (functional independence measure) and secondary clinical outcome parameters in both study groups at the end of sedation and at ICU discharge.

AIM 2 - Hypothesis: EMS prevents thick filament loss.
Test: The extent of thick filament loss will be visualised by histopathological staining and electron microscopy and will be compared between both study groups. Regulation of atrophy gene expression (MURF-I and Atrogin) will be investigated.

AIM 3 - Hypothesis: EMS improves systemic insulin sensitivity as well as oxidative metabolism of skeletal muscles in the intervention group.
Test: We will investigate key molecules of insulin signalling, MAP-kinase and AMP-kinase in muscle biopsies by Real Time PCR and Western blotting. We will perform RT-PCR studies on the expression pattern of key mitochondrial genes as well as western blots of voltage-dependent anion channels of the outer mitochondrial membrane (VDAC) indicating mitochondrial muscle mass and will compare these parameters between the intervention and control group.

AIM 4 - Hypothesis: EMS promotes activation of specific metabolic pathways. Thus, the metabolic adaptations may be critical for the development of CIM in critically ill patients and the metabolic profile may thus serve as a reliable biomarker for disease prediction.
Test: Metabolite profiling will be performed on a Pegasus 3 time-of-flight mass spectrometer (Leco) equipped with a Direct Thermal Desorption injector (ATAS GL International) coupled to an HP 5890 gas chromatograph and a dual-arm autosampler with automatic de-vitalisation and liner exchange. Chromatograms will be processed using Leco ChromaTOF software (version 3.25) and peaks with signal to noise ratios >10 and will be exported before using an in-house developed algorithm. Mass spectra will be compared to the in-house mass spectral library according to mass spectral similarity and retention. Principal component analysis (PCA) will be performed on the obtained data to illustrate disparities between intervention and control group on metabolite levels.

Ethics approval

Charite - Berlin Medical University (Charite - Universitätsmedizin Berlin) Ethics Committee approved in May 2010 (ref: EA2/041/10)

Study design

Randomised controlled observer blind clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Intensive Care Unit-acquired weakness (ICUAW)/Critical illness myopathy (CIM)

Intervention

Patients allocated to the intervention group will receive EMS treatment of M. quadriceps femoris (M. vastus lateralis and M. rectus femoris), M. tibialis anterior, M. biceps brachii, M. triceps brachii, M. brachioradialis and ventral auxiliary muscles (Th9 - Th11) twice per day.

Patients allocated to the control group will receive sham stimulation of respective muscles twice per day by electrode placement without application of electrical current.

Within the intervention group, the applied electrical current depends on visible or palpable contracation or patient discomfort (maximum current applied: 70mA, maximum duration of intervention: 28 days).

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Clinical: muscle strength assessd by MRC score after the end of sedation and functional impairment at ICU discharge as indicated by FIM
2. Molecular: incidence of histologically proven CIM, measured during the study enrolment period

Secondary outcome measures

1. Clinical (assessed during the study enrolment period):
1.1. Ventilator-free days
1.2. ICU stay
1.3. EMG/ENG
1.4. Weaning failure
2. Molecular (analysed once patient enrolment has ended):
2.1. Signalling pathways (insulin/IGF-1, AMP-Kinase, MAP-Kinase)
2.2. Tissue metabolism
2.3. Atrophy gene regulation
2.4. Mitochondrial function
2.5. Caveolae dynamics

Overall trial start date

01/10/2010

Overall trial end date

30/09/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adults with a Sequential Organ Failure Assessment (SOFA) score greater than or equal to 9
2. Mechanical ventilation
3. Written informed consent of legal proxy
4. Aged greater than 18 years, either sex

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

80

Participant exclusion criteria

1. Patients with mechanical ventilation and SOFA less than or equal to 9 for more than 72 hours prior study screening
2. Age less than 18 years
3. No written informed consent by legal proxy
4. Pre-existing neuromuscular disorder
5. Coagulation disorder refractory to therapy
6. Pregnancy
7. Poor prognosis with expected death within the next hours or days

Recruitment start date

01/10/2010

Recruitment end date

30/09/2013

Locations

Countries of recruitment

Germany

Trial participating centre

CC7
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

Research organisation

Website

http://www.charite.de

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 Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany) (ref: No.192/2, 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

Publication citations

Additional files

Editorial Notes