Spinal Interneuron Excitability in ALS

NCT02429492 | Completed

• 2 other identifiers: C14-212014-A01240-47
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

Amyotrophic lateral sclerosis (ALS) is due to neurodegeneration of upper and lower motor neurons, leading to muscle atrophy, paralysis and death. However, there is growing evidence that interneurons involved in the gain regulation of spinal motoneuron (lower motor neurons) and in sensorimotor integration may participate in the pathogenesis of ALS. While sensory afferents in the peripheral nerve are traditionally thought to be unaffected at the beginning of the disease, diffusion MRI has revealed degeneration and demyelination of the posterior columns in the spinal cord of patients recently diagnosed with ALS, and there are sporadic reports of sensory involvement. Early alteration of the sensorimotor integration could participate to the degeneration of motor neurons and interneurons. The goal of the project is to further investigate sensorimotor integration at spinal level in human patients recently diagnosed with ALS, and to study whether an interneuron pathology could participate in ALS pathogenesis. Our project has first an interest for the fundamental research aiming at increasing basic knowledge of pathophysiology of ALS, and specifically on the functional effects of the underlying neurodegenerative mechanisms. By testing the excitability of spinal interneurons in patients recently diagnosed, and by doing so for clinically uninvolved muscles, we will be able to evaluate whether an interneuron pathology could be involved in ALS. Our results will help to understand better the chain reactions in the neurodegenerative processes that dramatically evolve until the death of all motor neurons. Our project has also an interest for the development of therapeutic approaches for ALS. Indeed, our methods will help to determine specific electrophysiological biomarkers that will help to evaluate quantitatively spinal and corticospinal neural processes: their changes during the course of the disease (follow-up study), the effect of therapeutic agents and/or rehabilitation methods on their excitability, and their repercussions on motor neuron activity (evaluation of therapeutics). Lastly, our methods could be tested in other neuromuscular diseases to determine possible differences in spinal neural activity. Indeed, the motor dysfunction common to several neuromuscular diseases can make it difficult to make a definitive diagnosis. The development of specific biomarkers is crucial for an early diagnosis, and to evaluate the best treatment for the patients as rapidly as possible.

Conditions

ALS

Keywords

Pathophysiology; Spinal interneurons; Electrophysiology; EMG; transcranial magnetic stimulation (TMS)

Outcome Measures

Primary Outcomes (1)

• Excitability of spinal neurons

  Electromyogram (EMG) reflects the activity of spinal motoneurons which is controlled by several spinal interneurons. EMG recordings will be conditioned by electrical, magnetic or mechanical stimuli to activate spinal interneurons that controlled motoneurons and thus influence the EMG recordings. The resulting changes in EMG activity will be quantified by calculating the EMG surface area or the change in peak-to-peak amplitude of evoked potentials. 2 visits will be devoted to cervical interneurons controlling upper limbs and the 2 other visits, to lumbar interneurons controlling lower limbs. Surface areas and amplitude in ALS patients will be compared to controls

  The participants will be invited to 4 sessions of EMG recordings whose duration will be of 2h30, within the month after inlcusion for ALS patients and within the year after inclusion for the healthy subjects

Study Arms (2)

ALS patients

EXPERIMENTAL

Patients with amyotrophy lateral sclerosis (ALS)

Device: Electrophysiology

Control subjetcs

EXPERIMENTAL

Neurologically intact subjects sex and age-matched to ALS patients

Device: Electrophysiology

Interventions

Electrophysiology DEVICE

EMG recordings conditioned by electrical peripheral nerve stimulation and/or transcranial magnetic stimulation

Also known as: EMG

ALS patients; Control subjetcs

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• speaking french
• signature of the written consent
• patients with ALS and no other motor neuron disease (ALS group)
• neurologically intact subjects (Control group)

You may not qualify if:

• pregnancy
• contraindication to TMS

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Hopital Pitie Salpetriere

Paris, 75013, France

Location

Related Publications (3)

• Turner MR, Kiernan MC. Does interneuronal dysfunction contribute to neurodegeneration in amyotrophic lateral sclerosis? Amyotroph Lateral Scler. 2012 May;13(3):245-50. doi: 10.3109/17482968.2011.636050. Epub 2012 Mar 16.

  PMID: 22424125 BACKGROUND

• Sangari S, Peyre I, Lackmy-Vallee A, Bayen E, Pradat PF, Marchand-Pauvert V. Transient increase in recurrent inhibition in amyotrophic lateral sclerosis as a putative protection from neurodegeneration. Acta Physiol (Oxf). 2022 Apr;234(4):e13758. doi: 10.1111/apha.13758. Epub 2022 Jan 23.

  PMID: 34981890 RESULT

• Marchand-Pauvert V, Peyre I, Lackmy-Vallee A, Querin G, Bede P, Lacomblez L, Debs R, Pradat PF. Absence of hyperexcitability of spinal motoneurons in patients with amyotrophic lateral sclerosis. J Physiol. 2019 Nov;597(22):5445-5467. doi: 10.1113/JP278117. Epub 2019 Oct 26.

  PMID: 31523813 RESULT

Related Links

• research team web site

Study Officials

• Pierre-François Pradat, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2014
• First Posted: April 29, 2015
• Study Start: November 16, 2015
• Primary Completion: September 7, 2021
• Study Completion: September 7, 2021
• Last Updated: January 12, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 2018-2019

Locations

FR (1)