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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Swiss Paraplegic Centre Nottwil
Information provided by (Responsible Party):
Bertrand LEGER, Clinique Romande de Readaptation
ClinicalTrials.gov Identifier:
NCT01470950
First received: September 21, 2011
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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 Intervention
Spinal Cord Injuries
Muscle Atrophy
Procedure: Motionmaker

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Characterization of the Changes in the Signalling Pathways During Spinal Cord Injury-induced Skeletal Muscle Atrophy

Resource links provided by NLM:


Further study details as provided by Clinique Romande de Readaptation:

Primary Outcome Measures:
  • Signaling pathways in human muscles after spinal cord injury [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Muscle biopsy of the vastus lateralis


Secondary Outcome Measures:
  • Muscle strength [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    leg circumference and power output on the Motionmaker

  • Spacity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Reduction of spasticity


Estimated Enrollment: 28
Study Start Date: May 2010
Estimated Study Completion Date: December 2015
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MotionMaker Training
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

Detailed Description:

Measures:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01470950

Locations
Switzerland
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
Investigators
Principal Investigator: Bertrand Léger, PhD CRR Sion
Principal Investigator: Michael E Baumberger, MD Swiss Paraplegic Centre Nottwil
  More Information

No publications provided

Responsible Party: Bertrand LEGER, PhD, Scientific Collaborator, Clinique Romande de Readaptation
ClinicalTrials.gov Identifier: NCT01470950     History of Changes
Other Study ID Numbers: MMStudy
Study First Received: September 21, 2011
Last Updated: January 28, 2014
Health Authority: Switzerland: Ethical Committee of Lucerne

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

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

ClinicalTrials.gov processed this record on July 24, 2014