Characterization of the Changes in the Signalling Pathways During Spinal Cord Injury-induced Skeletal Muscle Atrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01470950
Recruitment Status : Unknown
Verified February 2015 by Bertrand LEGER, Clinique Romande de Readaptation.
Recruitment status was:  Active, not recruiting
First Posted : November 11, 2011
Last Update Posted : February 5, 2015
Swiss Paraplegic Centre Nottwil
Information provided by (Responsible Party):
Bertrand LEGER, Clinique Romande de Readaptation

Brief Summary:

Atrogin-1 and muscle RING finger-1 are skeletal muscle specific genes, with ubiquitin ligase activities, that are upregulated during muscle atrophy in mice. The Akt/GSK3 and Akt/mTOR pathways are involved in muscle hypertrophy in mice. Recent studies by the investigators team and others have demonstrated the implication of these signalling pathways in the control of muscle mass in humans. However no study has yet investigated the involvement of these systems in the early stages of spinal cord injury induced human skeletal muscle atrophy.

The investigators propose to investigate the level of expression of the different components of the ubiquitin-proteasome system together with the level of expression and activity of the Akt/mTOR and Akt/GSK3 signalling pathways after SCI in humans during the first months following the injury.

A second aim of this project is to assess if a novel apparatus of electrical stimulation which generate movements by closed-loop electrical muscle stimulation may improve strength and muscle mass in these patients.

The patients will be recruited jointly at the Clinique Romande de Réadaptation (CRR) in Sion and the Swiss paraplegic centre in Nottwil. They will be randomly divided into two groups, a first group of patients will undergo a conventional treatment of rehabilitation while a second set of patients will be treated using a brand new system of electro-stimulation called MotionMaker TM. Biopsies will be obtained in the first weeks after admission; two other biopsies will be taken respectively 3 and 6 months post-lesion.

Our results will provide an increased understanding of the molecular mechanisms contributing to skeletal muscle atrophy during the early stages following SCI and a characterization of the impact of endurance training in the no more voluntary innervated muscle. Moreover this study will also investigate the potential improvement in the rehabilitation process by using a new system of electro-stimulation.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Muscle Atrophy Procedure: Motionmaker Not Applicable

Detailed Description:


For each group, the muscle biopsies will be divided into 3 samples which will be used for a) real-time PCR to quantify the gene expression of the different components of the ubiquitin-proteasome system (Atrogin-1, MuRF1, Nedd4, UBB and Psma) b) Western blotting, using anti-phospho-site specific antibodies to quantify the activities of the Akt/GSK3 and Akt/mTOR pathways and of their downstream regulators of protein synthesis, eIF2B, p70S6K and PHAS-1/4E-BP1and c) fiber type analysis to quantify the variation in MHC expression.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Characterization of the Changes in the Signalling Pathways During Spinal Cord Injury-induced Skeletal Muscle Atrophy
Study Start Date : May 2010
Actual Primary Completion Date : December 2013
Estimated Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: MotionMaker Training
Device description: MotionMaker™ is a stationary robotic system for the active mobilization of the lower limbs. With its proprietary 'Closed-Loop' technology, it is a novel and exciting development that offers a truly interactive patient training system Training 3 times a week with MotionMaker device together with conventional treatment
Procedure: Motionmaker
3 times per week, FES Training on the Motionmaker device, for 6 months

Primary Outcome Measures :
  1. Signaling pathways in human muscles after spinal cord injury [ Time Frame: 6 months ]
    Molecular adaptations will be assessed from biopsies of the Vastus Lateralis muscle. Quantitative PCR method will allow to measure mRNA expression levels while proteins quantification will be performed by Western Blot analyses.

Secondary Outcome Measures :
  1. Muscle strength [ Time Frame: 6 months ]
    Improvement of muscle strenght

  2. Spacity [ Time Frame: 6 months ]
    Reduction of spasticity

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • acute, motor complete SCI
  • lesion level C5-T12

Exclusion Criteria:

  • diabetes type I
  • pregnancy
  • oral anti-coagulation
  • osteosyntheses of the femur
  • hepatitis B,C or D
  • HIV

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01470950

Swiss Paraplegic Centre
Nottwil, Lucerne, Switzerland, 6207
Clinique Romande de Réadaption
Sion, Valais, Switzerland, 1951
Sponsors and Collaborators
Clinique Romande de Readaptation
Swiss Paraplegic Centre Nottwil
Principal Investigator: Bertrand Léger, PhD CRR Sion
Principal Investigator: Michael E Baumberger, MD Swiss Paraplegic Centre Nottwil

Responsible Party: Bertrand LEGER, PhD, Scientific Collaborator, Clinique Romande de Readaptation Identifier: NCT01470950     History of Changes
Other Study ID Numbers: MMStudy
First Posted: November 11, 2011    Key Record Dates
Last Update Posted: February 5, 2015
Last Verified: February 2015

Keywords provided by Bertrand LEGER, Clinique Romande de Readaptation:
Functional Electrical Stimulation
Signalling Pathways

Additional relevant MeSH terms:
Wounds and Injuries
Spinal Cord Injuries
Muscular Atrophy
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms