Amyotrophic Lateral SclerosisSTRATALSNCT05358431
Stratification of Presymptomatic Amyotrophic Lateral Sclerosis: the Development of Novel Imaging Biomarkers
A study testing Neuroimaging and electrophysiology in people with Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder with no effective disease-modifying therapies at present. The disease is sporadic in 90 % of the ALS patients. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Neuroimaging and electrophysiology
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- 21 Jul 2022to 21 Feb 2026
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients fulfilling the El Escorial criteria for probable or definite ALS
- Presence of a C9orf72 mutation
Who cannot join
- Contraindication to MRI and TMS
- Impossibility to stay in decubitus during 1 hour,
- For women, childbearing or breastfeeding
- For women of childbearing potential: positive HCG test or positive urine pregnancy test
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
ICM, GH Pitié-Salpêtrière
Paris, 75013
Pierre-François Pradat, MD, 01 42 16 24 71 ext. +33, pierre-francois.pradat@aphp.fr
About this study
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder with no effective disease-modifying therapies at present. The disease is sporadic in 90 % of the ALS patients. Up to 40 % familial ALS cases and up to 25% of familial frontotemporal dementia (FTD) are caused by autosomal dominant GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. The presymptomatic phase of the disease represents a unique opportunity to evaluate mechanisms of disease propagation, characterise patterns of anatomical spread, validate staging systems and appraise the comparative sensitivity profile of emerging imaging modalities. Very few spinal cord imaging studies currently exist in ALS despite their potential to characterise both the lower and upper motor neuron components of the disease. This prospective longitudinal study of asymptomatic and symptomatic c9orf72 hexanucleotide carriers will use a purpose-designed spinal and brain imaging protocol and comprehensive clinical, genetic, electrophysiological and neuropsychological profiling. Newly developed imaging techniques such as spinal cord NODDI, spinal fMRI, quantitative thoracic cord imaging will be implemented in addition to established spinal cord and brain imaging techniques.
Read the detailed description
The main objective is to study the disease trajectory from the presymptomatic to the symptomatic phase of ALS. We will study a population of asymptomatic subjects carrying an autosomal dominant GGGGCC hexanucleotide repeat expansions in the C9orf72 gene that is the most frequent mutation in familial cases of ALS. The changes will be compared to a population of healthy controls. We have selected two populations of healthy controls to take into account the possible interaction with the genetic background. The first population of controls will consist in subjects sharing the same genetic background than the presymptomatic subjects, e.g. non mutated subjects related to C9 + symptomatic carriers. The second population will consist in healthy individuals coming from the general population. We will compare the presymptomatic changes to changes occurring at the symptomatic phase by studying a group of patients with symptomatic ALS. We will use a multimodal longitudinal approach combing spinal and brain imaging protocol and comprehensive clinical, genetic, electrophysiological and neuropsychological profiling.
Secondary objectives
- Comparison of the changes in young presymptomatic subjects (less than 40 years) vs older patients
- Changes over time in ALS patients : MRI metrics, electrophysiological parameters and neuropsychological impairment
- The development of prognostic indicators based on spinal cord/ brain imaging and electrophysiology to foretell phenotypic manifestation (such as DFT or ALS) and age of onset.
- The integrative evaluation of brain-cord interactions, comparing the relative detection sensitivity of spinal and cerebral imaging measures.
- Assessing the imaging evidence for the prevailing 'corticofugal spread' or 'dying-forward' theory based on longitudinal spinal cord and cerebral data.
- Characterizing associations between imaging and electrophysiology metrics of upper motor neuron (UMN) and LMN (lower motor neuron) integrity; correlation of segmental grey matte metrics to MUNIX; TMS to corticospinal tract measures
- Assessing whether longitudinal cerebral and spinal cord imaging data are consistent with sequential TDP-43 pathological staging systems.
- The cross-validation of newly developed cord techniques; NODDI, fMRI, thoracic cord imaging with established structural and diffusion imaging metrics and electrophysiology measures.
- Correlations between imaging, electrophysiology and neuropsychological metrics
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Neuroimaging and electrophysiology
- Keywords
- MRI, ALS, FTD, MUNE, C9orfF72, presymptomatic
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuroimaging and electrophysiologyOther
Brain and spinal cord MRI, transcranial magnetic stimulation; Motor Unit Number Estimation, EEG
| Study group | Role | What they receive |
|---|---|---|
| participants | Experimental | Patients fulfilling the El Escorial criteria for probable or definite ALS with a C9orf72 mutation or asymptomatics being a first-degree to a person carrying a C9orf72 mutation or Healthy controls Receives: Other: Neuroimaging and electrophysiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional and structural quantitative imaging
Changes in resting state spinal cord MRI (fMRI) signal in presymptomatic and symptomatic ALS patients compared to controls
Measured: 6 months
Secondary outcomes (3)
Electromyography with MUNE
Difference between electrophysiological MUNE between the first and last visit
Measured: 6 months
TMS
Difference between electrophysiological TMS between the first and last visit
Measured: 6 months
EEG
Difference between electrophysiological "Resting state (rs-)EEG" ,alpha (7-13 Hz), beta (13-40 Hz) and gamma bands (40-200 Hz) between the first and last visit
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start21 Jul 2022
- Primary completion21 Feb 2026 (estimated)
- Study completion21 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05358431
- Sponsor's protocol ID
- APHP211449
- Other IDs
- 2022-A00083-40
- Acronym
- STRATALS
- Status last verified
- Feb 2024
- First submitted
- 17 Feb 2022
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Saracino D, Cipriano L, Houot M, Querin G, Rinaldi D, Rametti-Lacroux A, Wallon D, Gerardin E, Couratier P, Boncoeur MP, Lebouvier T; PREV-DEMALS and STRATALS study groups; Colliot O, Pradat PF, Migliaccio R, Le Ber I. Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease. Alzheimers Dement. 2025 Dec;21(12):e70902. doi: 10.1002/alz.70902.
PubMed 41366786
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stratification of Presymptomatic Amyotrophic Lateral Sclerosis: the Development of Novel Imaging Biomarkers
- ClinicalTrials.gov ID
- NCT05358431
- Acronym / sponsor ID
- STRATALS / APHP211449
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- MRI, ALS, FTD, MUNE, C9orfF72, presymptomatic
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 21 Feb 2026 (estimated)
- Study completion
- 21 Feb 2026 (estimated)
- First posted
- 3 May 2022 (actual)
- 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 a relentlessly progressive neurodegenerative disorder with no effective disease-modifying therapies at present. The disease is sporadic in 90 % of the ALS patients. Up to 40 % familial ALS cases and up to 25% of familial frontotemporal dementia (FTD) are caused by autosomal dominant GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. The presymptomatic phase of the disease represents a unique opportunity to evaluate mechanisms of disease propagation, characterise patterns of anatomical spread, validate staging systems and appraise the comparative sensitivity profile of emerging imaging modalities. Very few spinal cord imaging studies currently exist in ALS despite their potential to characterise both the lower and upper motor neuron components of the disease. This prospective longitudinal study of asymptomatic and symptomatic c9orf72 hexanucleotide carriers will use a purpose-designed spinal and brain imaging protocol and comprehensive clinical, genetic, electrophysiological and neuropsychological profiling. Newly developed imaging techniques such as spinal cord NODDI, spinal fMRI, quantitative thoracic cord imaging will be implemented in addition to established spinal cord and brain imaging techniques.
Detailed description
The main objective is to study the disease trajectory from the presymptomatic to the symptomatic phase of ALS. We will study a population of asymptomatic subjects carrying an autosomal dominant GGGGCC hexanucleotide repeat expansions in the C9orf72 gene that is the most frequent mutation in familial cases of ALS. The changes will be compared to a population of healthy controls. We have selected two populations of healthy controls to take into account the possible interaction with the genetic background. The first population of controls will consist in subjects sharing the same genetic background than the presymptomatic subjects, e.g. non mutated subjects related to C9 + symptomatic carriers. The second population will consist in healthy individuals coming from the general population. We will compare the presymptomatic changes to changes occurring at the symptomatic phase by studying a group of patients with symptomatic ALS. We will use a multimodal longitudinal approach combing spinal and brain imaging protocol and comprehensive clinical, genetic, electrophysiological and neuropsychological profiling.
Secondary objectives
- Comparison of the changes in young presymptomatic subjects (less than 40 years) vs older patients
- Changes over time in ALS patients : MRI metrics, electrophysiological parameters and neuropsychological impairment
- The development of prognostic indicators based on spinal cord/ brain imaging and electrophysiology to foretell phenotypic manifestation (such as DFT or ALS) and age of onset.
- The integrative evaluation of brain-cord interactions, comparing the relative detection sensitivity of spinal and cerebral imaging measures.
- Assessing the imaging evidence for the prevailing 'corticofugal spread' or 'dying-forward' theory based on longitudinal spinal cord and cerebral data.
- Characterizing associations between imaging and electrophysiology metrics of upper motor neuron (UMN) and LMN (lower motor neuron) integrity; correlation of segmental grey matte metrics to MUNIX; TMS to corticospinal tract measures
- Assessing whether longitudinal cerebral and spinal cord imaging data are consistent with sequential TDP-43 pathological staging systems.
- The cross-validation of newly developed cord techniques; NODDI, fMRI, thoracic cord imaging with established structural and diffusion imaging metrics and electrophysiology measures.
- Correlations between imaging, electrophysiology and neuropsychological metrics
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| participants | Experimental | Other: Neuroimaging and electrophysiologyPatients fulfilling the El Escorial criteria for probable or definite ALS with a C9orf72 mutation or asymptomatics being a first-degree to a person carrying a C9orf72 mutation or Healthy controls |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients fulfilling the El Escorial criteria for probable or definite ALS
- Presence of a C9orf72 mutation
Key exclusion criteria (4 listed)
- Contraindication to MRI and TMS
- Impossibility to stay in decubitus during 1 hour,
- For women, childbearing or breastfeeding
- For women of childbearing potential: positive HCG test or positive urine pregnancy test
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 |
|---|---|---|
| Neuroimaging and electrophysiologyBrain and spinal cord MRI, transcranial magnetic stimulation; Motor Unit Number Estimation, EEG | Other | participants |
Primary outcome
Functional and structural quantitative imaging
Time frame: 6 months
Changes in resting state spinal cord MRI (fMRI) signal in presymptomatic and symptomatic ALS patients compared to controls
3 secondary outcomes
Electromyography with MUNE
Time frame: 6 months
TMS
Time frame: 6 months
EEG
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Derived from this study: PubMed 41366786Saracino D, Cipriano L, Houot M, Querin G, Rinaldi D, Rametti-Lacroux A, Wallon D, Gerardin E, Couratier P, Boncoeur MP, Lebouvier T; PREV-DEMALS and STRATALS study groups; Colliot O, Pradat PF, Migliaccio R, Le Ber I. Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease. Alzheimers Dement. 2025 Dec;21(12):e70902. doi: 10.1002/alz.70902.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neuroimaging and electrophysiology in people with Amyotrophic Lateral Sclerosis, run by Assistance Publique - Hôpitaux de Paris 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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 20 Feb 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pierre Francois PRADAT, MD, PH (1.42.16.24.71 ext. +33, pierre-francois.pradat@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional and structural quantitative imaging (time frame: 6 months). 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 NCT05358431, which also lists 1 linked publication.
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 20 Feb 2024.