ALSSpineBioMarkNCT02429492
Spinal Interneuron Excitability in ALS
A study testing Electrophysiology in people with ALS, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- ALS
- What is being tested?
- Electrophysiology
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteFrance
- Study dates
- 16 Nov 2015to 7 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- speaking french
- signature of the written consent
- patients with ALS and no other motor neuron disease (ALS group)
- neurologically intact subjects (Control group)
Who cannot join
- pregnancy
- contraindication to TMS
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- ALS
- Being tested
- Electrophysiology
- Keywords
- Pathophysiology, Spinal interneurons, Electrophysiology, EMG, transcranial magnetic stimulation (TMS)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElectrophysiologyDevice
Also called EMG
EMG recordings conditioned by electrical peripheral nerve stimulation and/or transcranial magnetic stimulation
| Study group | Role | What they receive |
|---|---|---|
| ALS patients | Experimental | Patients with amyotrophy lateral sclerosis (ALS) Receives: Device: Electrophysiology |
| Control subjetcs | Experimental | Neurologically intact subjects sex and age-matched to ALS patients Receives: Device: Electrophysiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study start16 Nov 2015
- Primary completion7 Sep 2021
- Study completion7 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ALSStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Pierre-François Pradat, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02429492
- Sponsor's protocol ID
- C14-21
- Other IDs
- 2014-A01240-47
- Acronym
- SpineBioMark
- Status last verified
- Mar 2025
- First submitted
- 29 Dec 2014
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: the results will be published in international peer-reviewed journals
Publications
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.
PubMed 22424125Sangari 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.
PubMed 34981890Marchand-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.
PubMed 31523813
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Biomarkers of Spinal Neural Activity: Study in Healthy Subjects Matched to ALS Patient Group
- ClinicalTrials.gov ID
- NCT02429492
- Acronym / sponsor ID
- SpineBioMark / C14-21
- Conditions
- ALS
- Keywords
- Pathophysiology, Spinal interneurons, Electrophysiology, EMG, transcranial magnetic stimulation (TMS)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 16 Nov 2015 (actual)
- Primary completion
- 7 Sep 2021 (actual)
- Study completion
- 7 Sep 2021 (actual)
- First posted
- 29 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALS patients | Experimental | Device: ElectrophysiologyPatients with amyotrophy lateral sclerosis (ALS) |
| Control subjetcs | Experimental | Device: ElectrophysiologyNeurologically intact subjects sex and age-matched to ALS patients |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- speaking french
- signature of the written consent
- patients with ALS and no other motor neuron disease (ALS group)
- neurologically intact subjects (Control group)
Key exclusion criteria (2 listed)
- pregnancy
- contraindication to TMS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ElectrophysiologyAlso: EMGEMG recordings conditioned by electrical peripheral nerve stimulation and/or transcranial magnetic stimulation | Device | ALS patients, Control subjetcs |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Background: PubMed 22424125Turner 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.
- Results publication: PubMed 34981890Sangari 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.
- Results publication: PubMed 31523813Marchand-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.
- research team web siteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. the results will be published in international peer-reviewed journals
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre-François Pradat, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electrophysiology in people with ALS, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02429492, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.