Study of miRNA Expression Pattern as Diagnostic and Prognostic Biomarker in Amyotrophic Lateral Sclerosis

NCT01992029 | Terminated

• 1 other identifier: CHUBX 2012/13
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The principal goal is to demonstrate that a specific pattern of microRNA (miRNA) expression can be correlated with the definite diagnostic of Amyotrophic Lateral Sclerosis (ALS). The investigators will use biological sample (from muscle biopsy, Cerebrospinal Fluid (CSF) and blood sample) collected in three control populations: definite ALS patients according to El Escorial diagnostic criterion, control patients without any neurological disease having an orthopedic surgery for shoulder disease, and control patient explored for peripheral neuropathy and myopathy. A second goal will correlate the miRNA pattern to the severity and/or progression rate of the motor neurons define as the progression rate of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) score/year.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Keywords

ALS; miRNA; biomarker; monocentric observational study

Outcome Measures

Primary Outcomes (1)

• miRNA expression

  miRNA expression pattern in ALS patients compared to control patients.

  At inclusion (day 0)

Secondary Outcomes (3)

• miRNA evolution

  12 months after inclusion

• miRNA expression pattern in different ALS patients compared to control patients predictive of the clinical phenotype and of the progression of the disease.

  Day 0 (inclusion)

• Difference in diffusivity parameters of MRI

  At inclusion (Day 0) and 8 month after inclusion

Study Arms (4)

ALS Patients

Other: Clinical evaluation; Procedure: Muscular biopsy; Procedure: Lumbar puncture; Procedure: Blood sampling; Device: Cervical spinal cord and brain MRI

Control patients suffering from neuropathy

Other: Neurological assessments; Procedure: Neuro-muscular biopsy and lumbar puncture; Procedure: Blood sample; Device: Cervical spinal cord and brain MRI

Control patients suffering from myopathy

Other: Neurological assessments; Procedure: Muscular biopsy; Procedure: Blood sample; Device: Cervical spinal cord and brain MRI

Control subjects

control patients without any neurological disease having an orthopedic surgery for shoulder disease

Other: Neurological assessments; Procedure: Muscular biopsy; Procedure: Blood sample; Device: Cervical spinal cord and brain MRI

Interventions

Clinical evaluation OTHER

Clinical evaluation using MRC scale, Norris bulbar scale, ALSFRS score and respiratory evaluation ( Vital Capacity, PiMax and SNIP) at M0, M4, M8, M12

ALS Patients

Muscular biopsy PROCEDURE

Muscular biopsy at M0

ALS Patients

Lumbar puncture PROCEDURE

Lumbar puncture at M0 and M12

ALS Patients

Blood sampling PROCEDURE

Blood sampling at M0, M4, M4, M8 and M12

ALS Patients

Neurological assessments OTHER

Neurological assessments (MRC score and cognitive scales: MMS and BREF)

Control patients suffering from myopathy; Control patients suffering from neuropathy; Control subjects

Neuro-muscular biopsy and lumbar puncture PROCEDURE

Neuro-muscular biopsy and lumbar puncture for patients explored for peripheral neuropathy

Control patients suffering from neuropathy

Blood sample PROCEDURE

Blood sample for qRT PCR, detection and quantification for miRNA

Control patients suffering from myopathy; Control patients suffering from neuropathy; Control subjects

Cervical spinal cord and brain MRI DEVICE

ALS patients : MRI at inclusion and Month 8 Control patients suffering from neuropathy : MRI at inclusion and Month 8 Control patients suffering from myopathy : MRI at inclusion Control subjects : MRI at inclusion

ALS Patients; Control patients suffering from myopathy; Control patients suffering from neuropathy; Control subjects

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients suffering from ALS, neuropathy, myopathy or control subjects having a shoulder surgery during which they will have a muscle (deltoid) biopsy

You may qualify if:

• For ALS patients:
• Age between 45 and 70 years old
• Patients with definite criteria of ALS according to revised El Escorial criterion (1998).
• ALS Patients with a clinical motor impairment of the limbs +/- impairment of the bulbar muscles.
• Patients with a clinical motor impairment on the deltoid muscle (MRC score\<5)
• For control patients:
• Age between 45 and 70 years old
• Patients having an orthopedic surgery of the shoulder with a normal neurological examination
• Patients having a peripheral neuropathy with a motor component needing a biological blood sample, a lumbar puncture for CSF examination and a neuro-muscular biopsy for complete diagnostic
• Patients having a muscular myopathy needing a biological blood sample and a deltoid muscle biopsy for complete diagnostic.
• Patients affiliated to a governmental health plan

You may not qualify if:

• Patients not eligible for a muscle biopsy (anti-coagulation, anti aggregation or blood coagulation pathologies)
• Patients not eligible for lumbar puncture (anti-coagulation, anti aggregation or blood coagulation pathologies, recent spine surgery, acquired or congenital spine malformation, clinical signs of intracranial hypertension, cutaneous infection at the punction site).
• ALS patient with isolated bulbar symptoms
• Patients with a clinical syndrome of ALS-plus associating extra-pyramidal symptoms, cerebellar or spino-cerebellar syndromes autonomic disorders or ocular palsy.
• Patients with marked cognitive impairments (MMS\<24/30 or BREF\<14/18)
• Pregnant or breastfeeding women
• Patients with any neurological or non-neurological disorders interfering with the ALSFRS score
• Patients who could not express their consent
• Patients in emergency situation
• Patients under guardianship or judicial protection
• Pace maker, cochlear implant
• Spinal cord compression or trauma
• Spine surgery
• Spinal deformity
• Claustrophobia

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux

Bordeaux, 33000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood Cerebrospinal fluid muscle

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Spinal Puncture; Blood Specimen Collection

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)

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

Study Officials

• Anne-Cécile WIELANEK-BACHELET, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Rodolphe THIEBAUT, MD, PhD

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: November 25, 2013
• Study Start: June 17, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 22, 2015
• Last Updated: November 5, 2018

Record last verified: 2018-11

Locations

FR (1)