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

NCT01470950 | Unknown

• 1 other identifier: MMStudy
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Spinal Cord Injuries; Muscle Atrophy

Keywords

Functional Electrical Stimulation; Signalling Pathways

Outcome Measures

Primary Outcomes (1)

• Signaling pathways in human muscles after spinal cord injury

  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.

  6 months

Secondary Outcomes (2)

• Muscle strength

  6 months

• Spacity

  6 months

Study Arms (1)

MotionMaker Training

EXPERIMENTAL

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

Interventions

Motionmaker PROCEDURE

3 times per week, FES Training on the Motionmaker device, for 6 months

MotionMaker Training

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Clinique Romande de Readaptation: lead
• Swiss Paraplegic Research, Nottwil: collaborator

Study Sites (2)

Swiss Paraplegic Centre

Nottwil, Canton of Lucerne, 6207, Switzerland

Location

Clinique Romande de Réadaption

Sion, Valais, 1951, Switzerland

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Muscular Atrophy

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Bertrand Léger, PhD

  CRR Sion

  PRINCIPAL INVESTIGATOR

• Michael E Baumberger, MD

  Swiss Paraplegic Research, Nottwil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Scientific Collaborator

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: November 11, 2011
• Study Start: May 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2015
• Last Updated: February 5, 2015

Record last verified: 2015-02

Locations

CH (2)