Stratification of Presymptomatic Amyotrophic Lateral Sclerosis: the Development of Novel Imaging Biomarkers

NCT05358431 | Recruiting

• 2 other identifiers: APHP2114492022-A00083-40
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

MRI; ALS; FTD; MUNE; C9orfF72; presymptomatic

Outcome Measures

Primary Outcomes (1)

• Functional and structural quantitative imaging

  Changes in resting state spinal cord MRI (fMRI) signal in presymptomatic and symptomatic ALS patients compared to controls

  6 months

Secondary Outcomes (3)

• Electromyography with MUNE

  6 months

• TMS

  6 months

• EEG

  6 months

Study Arms (1)

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

Other: Neuroimaging and electrophysiology

Interventions

Neuroimaging and electrophysiology OTHER

Brain and spinal cord MRI, transcranial magnetic stimulation; Motor Unit Number Estimation, EEG

participants

Eligibility Criteria

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

You may qualify if:

• Age more than 18 years.
• Signature of a consent form for clinical, paraclinical and genetic assessment
• Fluent in French
• Affiliated to the French Security Healthcare System ("Sécurité Sociale")
• Absence of neurological comorbidity (stroke, tumor etc)
• Being a first-degree to a person carrying a C9orf72 mutation.
• Absence of proven clinical signs of FTD, ALS, language, praxic, memory disorders, Parkinsonian syndrome.
• Patients fulfilling the El Escorial criteria for probable or definite ALS
• Presence of a C9orf72 mutation

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

ICM, GH Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 41366786 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Neuroimaging

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Investigative Techniques

Central Study Contacts

Pierre Francois PRADAT, MD, PH

CONTACT

1.42.16.24.71; pierre-francois.pradat@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: May 3, 2022
• Study Start: July 21, 2022
• Primary Completion: February 21, 2026
• Study Completion: February 21, 2026
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)