Outcome Measures and Biomarkers in a Cohort of Spinal Muscular Atrophy Type III/ IV Patients

NCT04690998 | Active Not Recruiting

• 1 other identifier: 2020-54
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 11

Brief Summary

The "SMOB" project intends to contribute to fill the gap with reliable and operational outcome measures for type III and IV SMA. In analysing the reliability in imaging (spinal and muscular), electrophysiology analysis (MUNIX), and evaluate the evolution of respiratory function for 50 patients' cohort. The investigators would also take the opportunity to collect biologic samples in order to investigate genetic markers and to assess quality of life of patients by QoL-gNMD questionnaire. The investigators aim to build a database that will allow us to evaluate the effectiveness of a new therapy for adult SMA patients by studying the natural history of the disease. The investigators have distributed the various expertise in Work Package where several centers are involved. This study is original in that it evaluates the parameters of qMRI and MUNIX in correlation with blood biomarkers. To our knowledge, there are no quantitative MRI (spinal and muscular) biomarkers and/or electrophysiological (MUNIX technique) highlighted for tracking the progression of the adult form of SMA type III and IV. This pilot study would allow identification of predictive markers of the disease progression, and to have validated, sensitive to change and relevant measurement tools that could be used as endpoints in future therapeutic trials.

Conditions

Spinal Muscular Atrophy

Outcome Measures

Primary Outcomes (21)

• Clinical examination

  MFM-32 Score

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• VAS

  Pain, tiredness, depression

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Fatigue Severity Scale (FSS)

  Pain, tiredness, depression

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Muscle strength

  Hand grip , tibialis anterior, forearm and hands circumference, ankle dorsiflexion

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Timed test

  Walk 10 meters

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Timed test

  6 min walk

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Timed test

  30 sit to stand

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Pulmonary function test

  FVC, MIP, MEP

  Change from Baseline at 12 months and 24 months

• Quality of Life of patients

  QoL-gNMD

  Change from Baseline at 6 months, 12 months, 18 months, 24 months

• Blood samples

  Analysis of SMN copy number gene and protein

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of Neurofilament

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of phosphorylated Neurofilament

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of transcriptomics

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of proteomics

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of microRNA, circulatingRNA, DNA methylation, circulating DNA

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of microRNA

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of circulatingRNA

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of DNA methylation, circulating DNA

  Change from Baseline at 12 months and 24 months

• Blood samples

  Analysis of circulating DNA

  Change from Baseline at 12 months and 24 months

• MRI

  Muscular MRI

  Change from Baseline at 24 months

• MRI

  Spinal MRI

  Change from Baseline at 24 months

Study Arms (2)

Without treatment for SMA

OTHER

Patient that will not take treatment for SMA during the two years of the study.

Other: Blood Samples; Other: MRI

Under treatment for SMA

OTHER

Patient that will take treatment for SMA during the two years of the study

Other: Blood Samples; Other: MRI

Interventions

Blood Samples OTHER

Genetic, proteomic, neurofilament analysis

Under treatment for SMA; Without treatment for SMA

MRI OTHER

Spinal and muscular MRI

Under treatment for SMA; Without treatment for SMA

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women
• Between 18 and 70 years old
• Given written informed consent after being informed of the purpose, progress and potential risks

You may not qualify if:

• Concomitant impairment of central nervous system (for example cervical myelopathy)
• Homeless patients
• Deprived of their liberty by a court or administrative order or under guardianship
• Unable to understand the purpose and conditions of carrying out the study, unable to give consent

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (11)

Service de Neurologie,Hôpital Raymond-Poincaré

Garches, 92380, France

Location

Département de Neurologie - CHRU Lille

Lille, 59037, France

Location

Service ENMG - Pathologies neuromusculaires, centre de référence en pathologie neuromusculaire Rhône-Alpes, Centre de référence SLA

Lyon, 69677, France

Location

CHU Montpellier

Montpellier, 34090, France

Location

Service Laboratoire d'Explorations Fonctionnelles, Hôtel-Dieu, CHU Nantes

Nantes, 44093, France

Location

Centre de Référence des Maladies Neuromusculaires - Pôle Neurosciences Cliniques, CHU Nice

Nice, 06001, France

Location

Institut de Myologie

Paris, 75013, France

Location

Service de Neurologie - CHU Saint-Etienne

Saint-Etienne, 42055, France

Location

Service des Maladies Neurologiques Rares

Saint-Pierre, 97448, France

Location

Centre de référence des Maladies Neuromusculaires,Service de Neurologie, Hôpital de Hautepierre

Strasbourg, 67000, France

Location

Service de Neurologie et d'explorations fonctionnelles, Hôpital Pierre-Paul Riquet, Place du Docteur Baylac

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

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

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: December 31, 2020
• Study Start: July 13, 2021
• Primary Completion: October 8, 2023
• Study Completion: October 8, 2025
• Last Updated: August 6, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)