Muscular Biomarkers in Amyotrophic Lateral Sclerosis (METABOMU)

Metabolomics and Transcriptomics Approaches to Identify Muscular Biomarkers in Amyotrophic Lateral Sclerosis

The first objective is to find some biomarkers, or a profile of biomarkers of ALS to help to diagnosis. The second objective is to better understand the pathogenesis of this disease by the exploration of muscle, blood and satellite cells metabolomes and transcriptomes.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Samples

Detailed Description

Amyotrophic Lateral Sclerosis (ALS), the most common MND, is a fatal adult-onset neuromuscular disease. Due to clinical heterogeneity and absence of biological tools to diagnose ALS, the delay between the first symptoms and diagnosis averages 9-13 months. A group of pathophysiological processes, including oxidative stress and glutamate-mediated excitotoxicity contribute to cell death, but the triggering factor, the timing and the interaction of different cellular events await elucidation [2]. Unknown pathogenesis for most patients means few available treatments. The search for biomarkers that can aid diagnosis, characterize phenotype, define pathophysiology, identify endpoints in trials and measure disease progression is of utmost importance for the field. Some studies have advocated that muscle per se may be impaired by pathogenesis of the diseases. Muscle has been poorly studied and its central role in energetic metabolism suggests that this tissue, quite easily available, should be more analyzed to find biomarkers and to compare muscular metabolism with those of brain and overall body. Specific aims of our subjects are:

Specific aims are focused on:

1. the acquisition of metabolites profiles of the muscle, blood and satellite cells using an analytical platform enable a deep exploration. For that, the use of three analytical modalities (NMR, mass spectrometry coupled to GC or UPLC) ensures the best coverage of the metabolite population with a high range of concentration variability and molecular diversity.
2. the building of metabolites profiles models that discriminate pathological and control situations.
3. the identification of metabolites implicated in the discriminant model.
4. the generation of metabolism pathways hypothesis related to the discriminant model.
5. the acquisition of transcriptomics data to confirm and add complementary results to metabolomics data

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Tours, France, 37044
    • Service de chirurgie orthopédique et traumatologique, CHRU de TOURS
  • Tours, France, 37044
    • Service de Neurologie, CHRU de TOURS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Case group selection criteria:

Inclusion Criteria:

• Age ≥ 18 years and ≥ 75 years
• ALS according to the El Escorial criteria
• Patients affiliated to social security scheme
• Informed consent signed by the patient

Exclusion Criteria:

• Pregnant or breastfeeding women
• Contraindication to biopsy
• Contraindication to local anesthesia
• Treatment with oral or injectable anticoagulants, antiplatelet (except aspirin)
• Unbalanced Diabetes
• Systemic corticosteroid treatment
• Treatment against cramps or twitching may affect muscle metabolism

Control group selection criteria:

Inclusion Criteria:

• Age ≥ 18 years and ≥ 75 years
• No neuronal disease
• Patients affiliated to social security scheme
• Informed consent signed by the patient

Exclusion Criteria:

• Pregnant or breastfeeding women
• Contraindication to biopsy
• Treatment with oral or injectable anticoagulants, antiplatelet (except aspirin)
• Unbalanced Diabetes
• Systemic corticosteroid treatment
• Treatment against cramps or twitching may affect muscle metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Case group; The intervention, specific to the study, is to take samples at baseline on patients with Amyotrophic Lateral Sclerosis	Other: Samples; Blood samples, muscle biopsy
Other: Control group; The intervention, specific to the study, is to take samples at baseline on patients without neurological disease	Other: Samples; Blood samples, muscle biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic signature of muscle	Metabolomics profile using NMR and LC-HRMS	At baseline
Metabolic signature of blood	Metabolomics profile using NMR and LC-HRMS	At baseline
Metabolic signature of satellites cells	Metabolomics profile using NMR and LC-HRMS	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression levels of targeted genes using transcriptomics	Choice of genes based on results obtained by metabolomics approaches	At baseline

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Hélène BLASCO, MD, helene.blasco@univ-tours.fr

Publications and helpful links

General Publications

• Lanznaster D, Bruno C, Bourgeais J, Emond P, Zemmoura I, Lefevre A, Reynier P, Eymieux S, Blanchard E, Vourc'h P, Andres CR, Bakkouche SE, Herault O, Favard L, Corcia P, Blasco H. Metabolic Profile and Pathological Alterations in the Muscle of Patients with Early-Stage Amyotrophic Lateral Sclerosis. Biomedicines. 2022 Jun 2;10(6):1307. doi: 10.3390/biomedicines10061307.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2016
• Primary Completion (Actual): October 15, 2019
• Study Completion (Actual): December 9, 2019

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 27, 2016
• First Posted (Estimated): February 1, 2016

Study Record Updates

• Last Update Posted (Estimated): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Metabolomics; Transcriptomics; Muscle metabolism
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Epidemiologic Study Characteristics; Sampling Studies
• Other Study ID Numbers: PHAO15-HB-METABOMU; 2015-A01629-40 (Other Identifier: IdRCB); 151550B-31 (Other Identifier: ASNM); 2016-R3 (Other Identifier: CPP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO