Spinal Interneuron Excitability in ALS (SpineBioMark)

January 8, 2026 updated by: Institut National de la Santé Et de la Recherche Médicale, France

Electrophysiological Biomarkers of Spinal Neural Activity: Study in Healthy Subjects Matched to ALS Patient Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Given the all-or-none properties of neuromuscular junctions, the electromyogram (EMG) reflects the activity of spinal motoneurons. These neurons are the last order neurons in all neural pathways involved in motor control. Modification of the afferent neural activity, whatever its level (spinal or supraspinal), will affect the excitability of spinal motoneurons and thus EMG activity. Combined with electrical and/or magnetic stimulation of peripheral nerve and/or cortical structures, it is possible to test indirectly the excitability of corticospinal and spinal reflex pathways involved in human motor control. One of the novelties is that we will investigate the interneurons that are activated by motor axons or afferents inputs from affected muscles (distal musculature: hand/wrist or foot/ankle muscles), which control clinically unaffected muscles (proximal musculature: elbow or knee muscles). This has a threefold interest i) functional exploration of clinically unaffected muscles that are never evaluated in ALS patients, ii) to better interpret the EMG signal and to better elucidate the pathophysiological mechanisms underlying the change in EMG activity, and iii) to determine if interneuron pathology manifests before detectable change in the motoneuron. The conditioned EMG and threshold tracking methods will be used to evaluate the excitability of spinal interneurons in ALS patients, as compared to sex and age-matched healthy subjects.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Hopital Pitie Salpetriere

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • pregnancy
  • contraindication to TMS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ALS patients
Patients with amyotrophy lateral sclerosis (ALS)
Device: Electrophysiology
EMG recordings conditioned by electrical peripheral nerve stimulation and/or transcranial magnetic stimulation
Other Names:
  • EMG
Experimental: Control subjetcs
Neurologically intact subjects sex and age-matched to ALS patients
Device: Electrophysiology
EMG recordings conditioned by electrical peripheral nerve stimulation and/or transcranial magnetic stimulation
Other Names:
  • EMG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Excitability of spinal neurons
Time Frame: 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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Pierre-François Pradat, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2015

Primary Completion (Actual)

September 7, 2021

Study Completion (Actual)

September 7, 2021

Study Registration Dates

First Submitted

December 29, 2014

First Submitted That Met QC Criteria

April 24, 2015

First Posted (Estimated)

April 29, 2015

Study Record Updates

Last Update Posted (Estimated)

January 12, 2026

Last Update Submitted That Met QC Criteria

January 8, 2026

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • C14-21
  • 2014-A01240-47 (Other Identifier: Agence Nationale de la Sécurité des Médicaments)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

the results will be published in international peer-reviewed journals

IPD Sharing Time Frame

2018-2019

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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