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

Spinal Cord Injuries Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01470950
• Other study ID #: MMStudy
• Status: Active, not recruiting
• Phase: N/A
• First received: September 21, 2011
• Last updated: February 4, 2015
• Start date: May 2010
• Est. completion date: December 2015

Study information

• Verified date: February 2015
• Source: Clinique Romande de Readaptation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethical Committee of Lucerne
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. completion date: December 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Atrophy
• Muscle Atrophy
• Muscular Atrophy
• Spinal Cord Injuries

Intervention

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

Locations

Country	Name	City	State
Switzerland	Swiss Paraplegic Centre	Nottwil	Lucerne
Switzerland	Clinique Romande de Réadaption	Sion	Valais

Sponsors (2)

Lead Sponsor	Collaborator
Clinique Romande de Readaptation	Swiss Paraplegic Centre Nottwil

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Muscle strength	Improvement of muscle strenght	6 months	No
Secondary	Spacity	Reduction of spasticity	6 months	No