New Therapeutic Strategy in ALS Based on Metabolic Status and Associated Metabolic Pathways.

Not Applicable

Active, not recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Other: Samples; Other: Indirect calorimetry; Other: Electrical bioimpedance

• Registration Number: NCT03984708
• Lead Sponsor: University Hospital, Tours

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects central and peripheral motor neurons. None of the clinical trials conducted have been clearly successful and the disease remains incurable, putting patients' vital prognosis at risk in the medium term. An alteration of the basal metabolism leading to hypermetabolism has been described in several articles in the literature. The causes of this hypermetabolism and the precise exploration of the metabolic pathways involved are still poorly understood. The fibroblasts of ALS patients may be the site of some metabolic disturbances in this disease with a hypothetical specific basal metabolic profile. These cells are adapted to different metabolic explorations such as omnic approaches. Superficial skin biopsy followed by fibroblast culture can provide a considerable biobank. This cellular richness will allow us, in ALS patients and their controls, to perform metabolomic and lipidomic approaches, as well as the quantification transcriptomic approach."

Detailed Description

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects central and peripheral motor neurons. None of the clinical trials conducted have been clearly successful and the disease remains incurable, putting patients' vital prognosis at risk in the medium term. An alteration of the basal metabolism leading to hypermetabolism has been described in several articles in the literature. The causes of this hypermetabolism and the precise exploration of the metabolic pathways involved are still poorly understood. The fibroblasts of ALS patients may be the site of some metabolic disturbances in this disease with a hypothetical specific basal metabolic profile. These cells are adapted to different metabolic explorations such as omnic approaches. Superficial skin biopsy followed by fibroblast culture can provide a considerable biobank. This cellular richness will allow us, in ALS patients and their controls, to perform experiments for the quantification of metabolites by metabolic and lipidomic approaches, as well as the quantification of mRNAs and the rate of gene transcription by a transcriptomic approach.

Study Timeline

• Study First Submitted: 2019-06-04
• Study First Submitted QC: 2019-06-12
• Study First Posted: 2019-06-13
• Study Start: 2020-01-27
• Primary Completion: 2023-01-10
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-29
• Last Update Posted: 2023-11-30
• Study Completion: 2024-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• Age ≥ 18 years and ≥ 75 years
• ALS according to the El Escorial criteria
• Diagnosis of ALS < 6 months
• Symptoms onset < 2 years
• 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
• Dermatological diseases of the fibroblast
• Skin cancer
• Protection measure for guardianship or curatorship

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
• Dermatological diseases of the fibroblast
• Skin cancer
• Protection measure for guardianship or curatorship

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Case group	Electrical bioimpedance	The intervention, specific to the study, is to take samples at baseline on patients with Amyotrophic Lateral Sclerosis
Case group	Samples	The intervention, specific to the study, is to take samples at baseline on patients with Amyotrophic Lateral Sclerosis
Case group	Indirect calorimetry	The intervention, specific to the study, is to take samples at baseline on patients with Amyotrophic Lateral Sclerosis
Control group	Samples	The intervention, specific to the study, is to take samples at baseline on patients without neurological disease

Primary Outcome Measures

Name	Time	Method
Metabolic signature of blood : concentrations of molecules detected by mass spectrometry	Baseline	The metabolomic profile of blood represents the combination of the different molecules detected/quantified by mass spectrometry
Metabolic signature of fibroblast : concentrations of molecules detected by mass spectrometry	Baseline	The metabolomic profile of fibroblast represents the combination of the different molecules detected/quantified by mass spectrometry

Secondary Outcome Measures

Name	Time	Method
Expression levels of targeted molecules using transcriptomics	Baseline	Choice of molecules based on results obtained by metabolomics approaches

Trial Locations

Locations (2)

Neurology Department, University Hospital, Limoges; 🇫🇷 Limoges, France

Neurology Department, University Hospitla, Tours; 🇫🇷 Tours, France