Amyotrophic Lateral SclerosisMIRSLANCT01992029
Study of miRNA Expression Pattern as Diagnostic and Prognostic Biomarker in Amyotrophic Lateral Sclerosis
An observational study of Amyotrophic Lateral Sclerosis and ALS, run by University Hospital, Bordeaux at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 45 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, ALS
- What is being tested?
- Clinical evaluation, Muscular biopsy and Lumbar puncture
- Type of treatment
- Medical device, Surgery or procedure
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- 17 Jun 2014to 22 Oct 2015
- Phase
- Observational
- 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 45 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients suffering from ALS, neuropathy, myopathy or control subjects having a shoulder surgery during which they will have a muscle (deltoid) biopsy
Who may be able to join
- 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:
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- 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
- Clear and loyal consent form written and signed by the patient and the investigator ( before any exam and at least the day of inclusion)
Who cannot join
- 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
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- 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
- Metallic foreign body
- Pregnancy
- Vital capacity < 50 %
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Etude de l'Expression Des Micro-RNA Comme Biomarqueur Diagnostic et Pronostic Dans la Sclérose Latérale Amyotrophique
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.
Read the detailed description
Amyotrophic Lateral Sclerosis is an adult-onset neuro degenerative disease leading to muscle wasting, palsy and death due to respiratory failure within 3 to 5 years. The only effective drug (Riluzole) increases the life expectancy for about three months, knowing that on average, the diagnostic is given after a delay of one year in France. The identification of new biomarkers for early diagnostic is therefore of fundamental importance. This could improve the treatment efficacy but also give important clues about the prognostic, the rate of evolution and overall help identify new targets for future therapeutics. The investigators' goals are to find specific miRNA patterns expression associated to ALS in humans and use those patterns as diagnostic and prognostic tools.
miRNA are non-coding small fragments of RNA that binds mRNA and can down regulate their expression. In humans, around 700 miRNA have been so far identified. The role of miRNA in human pathology is well established in various types of cancer, but recent works have emphasize their role in neuro degenerative diseases and their expression profile can considered specific for Alzheimer, Parkinson and Huntington diseases. Very few data are currently available about their expression pattern in ALS. Previous studies have however shown that down regulating of some miRNA in spinal cord Moto neurons can trigger an ALS-like clinical phenotype. A more recent work on transgenic murine model SOD1 G93A has demonstrated the role of the specific miRNA206 in regulating the re-innervation processes at the neuro-muscular junction. Mi206 have the ability to promote the re-innervation process and therefore to slow the disease progression.
This research aimed to study the expression of more than 700 miRNA in four different groups (20 patients per group): ALS patients, normal control having a shoulder surgery during which they will have a muscle (deltoid) biopsy, patients explored for peripheral neuropathy with a blood sample, a lumbar puncture for CSF examination and neuro-muscular biopsy and patient explored for myopathy with a blood sample, a lumbar puncture for CSF examination and a muscular biopsy. The ALS group will be followed up every 4 months with ALSFRS scoring and blood sample and a second CSF sample only at M12. miRNA pattern expression will be compared and considered significant for a 2-fold change.
- Conditions
- Amyotrophic Lateral Sclerosis, ALS
- Being tested
- Clinical evaluation, Muscular biopsy, Lumbar puncture, Blood sampling, Neurological assessments
- Keywords
- ALS, miRNA, biomarker, monocentric observational study
- 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.
Clinical evaluationOther
Clinical evaluation using MRC scale, Norris bulbar scale, ALSFRS score and respiratory evaluation ( Vital Capacity, PiMax and SNIP) at M0, M4, M8, M12
Muscular biopsyProcedure or surgery
Muscular biopsy at M0
Lumbar punctureProcedure or surgery
Lumbar puncture at M0 and M12
Blood samplingProcedure or surgery
Blood sampling at M0, M4, M4, M8 and M12
Neurological assessmentsOther
Neurological assessments (MRC score and cognitive scales: MMS and BREF)
Neuro-muscular biopsy and lumbar punctureProcedure or surgery
Neuro-muscular biopsy and lumbar puncture for patients explored for peripheral neuropathy
Muscular biopsyProcedure or surgery
Muscular biopsy for patient explored for myopathy
Blood sampleProcedure or surgery
Blood sample for qRT PCR, detection and quantification for miRNA
Cervical spinal cord and brain MRIDevice
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
| Study group | Role | What they receive |
|---|---|---|
| ALS Patients | Not described Receives: Other: Clinical evaluation; Procedure: Muscular biopsy; Procedure: Lumbar puncture; Procedure: Blood sampling; Device: Cervical spinal cord and brain MRI | |
| Control patients suffering from neuropathy | Not described Receives: 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 | Not described Receives: 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 Receives: Other: Neurological assessments; Procedure: Muscular biopsy; Procedure: Blood sample; Device: Cervical spinal cord and brain MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
miRNA expression
miRNA expression pattern in ALS patients compared to control patients.
Measured: At inclusion (day 0)
Secondary outcomes (3)
miRNA evolution
Evolution of miRNA expression level in blood and CSF of ALS patients
Measured: 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.
Measured: Day 0 (inclusion)
Difference in diffusivity parameters of MRI
Difference in diffusivity parameters of MRI between ALS subjects and control groups
Measured: At inclusion (Day 0) and 8 month after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study start17 Jun 2014
- Primary completionOct 2015
- Study completion22 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne-Cécile WIELANEK-BACHELET, MD, Principal investigator, University Hospital, BordeauxRodolphe THIEBAUT, MD, PhD, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01992029
- Sponsor's protocol ID
- CHUBX 2012/13
- Acronym
- MIRSLA
- Status last verified
- Nov 2018
- First submitted
- 18 Nov 2013
- Last updated
- 5 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Etude de l'Expression Des Micro-RNA Comme Biomarqueur Diagnostic et Pronostic Dans la Sclérose Latérale Amyotrophique
- ClinicalTrials.gov ID
- NCT01992029
- Acronym / sponsor ID
- MIRSLA / CHUBX 2012/13
- Conditions
- Amyotrophic Lateral Sclerosis, ALS
- Keywords
- ALS, miRNA, biomarker, monocentric observational study
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 17 Jun 2014 (actual)
- Primary completion
- Oct 2015 (actual)
- Study completion
- 22 Oct 2015 (actual)
- First posted
- 25 Nov 2013 (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.
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.
Detailed description
Amyotrophic Lateral Sclerosis is an adult-onset neuro degenerative disease leading to muscle wasting, palsy and death due to respiratory failure within 3 to 5 years. The only effective drug (Riluzole) increases the life expectancy for about three months, knowing that on average, the diagnostic is given after a delay of one year in France. The identification of new biomarkers for early diagnostic is therefore of fundamental importance. This could improve the treatment efficacy but also give important clues about the prognostic, the rate of evolution and overall help identify new targets for future therapeutics. The investigators' goals are to find specific miRNA patterns expression associated to ALS in humans and use those patterns as diagnostic and prognostic tools.
miRNA are non-coding small fragments of RNA that binds mRNA and can down regulate their expression. In humans, around 700 miRNA have been so far identified. The role of miRNA in human pathology is well established in various types of cancer, but recent works have emphasize their role in neuro degenerative diseases and their expression profile can considered specific for Alzheimer, Parkinson and Huntington diseases. Very few data are currently available about their expression pattern in ALS. Previous studies have however shown that down regulating of some miRNA in spinal cord Moto neurons can trigger an ALS-like clinical phenotype. A more recent work on transgenic murine model SOD1 G93A has demonstrated the role of the specific miRNA206 in regulating the re-innervation processes at the neuro-muscular junction. Mi206 have the ability to promote the re-innervation process and therefore to slow the disease progression.
This research aimed to study the expression of more than 700 miRNA in four different groups (20 patients per group): ALS patients, normal control having a shoulder surgery during which they will have a muscle (deltoid) biopsy, patients explored for peripheral neuropathy with a blood sample, a lumbar puncture for CSF examination and neuro-muscular biopsy and patient explored for myopathy with a blood sample, a lumbar puncture for CSF examination and a muscular biopsy. The ALS group will be followed up every 4 months with ALSFRS scoring and blood sample and a second CSF sample only at M12. miRNA pattern expression will be compared and considered significant for a 2-fold change.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 | – | Other: Neurological assessments, Procedure: Muscular biopsy, Procedure: Blood sample, Device: Cervical spinal cord and brain MRIcontrol patients without any neurological disease having an orthopedic surgery for shoulder disease |
Who may qualify
- Ages
- 45 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients suffering from ALS, neuropathy, myopathy or control subjects having a shoulder surgery during which they will have a muscle (deltoid) biopsy
Key inclusion criteria (12 listed)
- 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)
- Age between 45 and 70 years old
Key exclusion criteria (18 listed)
- 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)
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 |
|---|---|---|
| Clinical evaluationClinical evaluation using MRC scale, Norris bulbar scale, ALSFRS score and respiratory evaluation ( Vital Capacity, PiMax and SNIP) at M0, M4, M8, M12 | Other | ALS Patients |
| Muscular biopsyMuscular biopsy at M0 | Procedure or surgery | ALS Patients |
| Lumbar punctureLumbar puncture at M0 and M12 | Procedure or surgery | ALS Patients |
| Blood samplingBlood sampling at M0, M4, M4, M8 and M12 | Procedure or surgery | ALS Patients |
| Neurological assessmentsNeurological assessments (MRC score and cognitive scales: MMS and BREF) | Other | Control patients suffering from myopathy, Control patients suffering from neuropathy, Control subjects |
| Neuro-muscular biopsy and lumbar punctureNeuro-muscular biopsy and lumbar puncture for patients explored for peripheral neuropathy | Procedure or surgery | Control patients suffering from neuropathy |
| Muscular biopsyMuscular biopsy for patient explored for myopathy | Procedure or surgery | Control patients suffering from myopathy, Control subjects |
| Blood sampleBlood sample for qRT PCR, detection and quantification for miRNA | Procedure or surgery | Control patients suffering from myopathy, Control patients suffering from neuropathy, Control subjects |
| Cervical spinal cord and brain MRIALS 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 | Device | ALS Patients, Control patients suffering from myopathy, Control patients suffering from neuropathy, Control subjects |
Primary outcome
miRNA expression
Time frame: At inclusion (day 0)
miRNA expression pattern in ALS patients compared to control patients.
3 secondary outcomes
miRNA evolution
Time frame: 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.
Time frame: Day 0 (inclusion)
Difference in diffusivity parameters of MRI
Time frame: At inclusion (Day 0) and 8 month after inclusion
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2018.
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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.
Anne-Cécile WIELANEK-BACHELET, MD principal investigator
University Hospital, Bordeaux
Rodolphe THIEBAUT, MD, PhD study chair
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyotrophic Lateral Sclerosis and ALS, run by University Hospital, Bordeaux 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 12 inclusion and 18 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: stopped early, as of the sponsor's last update on 5 Nov 2018. 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 was stopped early. Results are not available in the source record.
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?
miRNA expression (time frame: At inclusion (day 0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2018.