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Microglial Activation Role In ALS (MARIA) (MARIA)

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Withdrawn
Phase
Early Phase 1
Locations
France
Study Type
Interventional
Intervention
[18F]DPA-714 PET
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Amyotrophic Lateral Sclerosis focused on measuring amyotrophic lateral sclerosis disease, PET, microglial activation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed informed consent
  • Age ≥ 18 years old
  • Patient with probable or definite sporadic Amyotrophic Lateral Sclerosis (ALS) form according to the modified criteria of El Escorial
  • Treated with riluzole 2 weeks
  • Evolution less than 18 months
  • Mini-Mental State Examination (MMS) score ≥ 26 and Frontal Assessment Battery (FAB) (normal)
  • Affiliated to a social security system

Exclusion Criteria:

  • Another unbalanced progressive pathology
  • Vascular diseases (hypertension, diabetes, smoking, dyslipidemia) unbalanced
  • Forced vital capacity <75%
  • Weight loss> 10% of the weight before disease
  • Status "low affinity binder" or "mixed affinity binder", the TSPO respect to the [18 F] DPA-714, which can interfere with the process of neuroinflammation: drugs with anti-inflammatory drugs (NSAIDs, corticosteroids, azathioprine, anti-tumor necrosis factor (TNF), antibiotics)
  • Benzodiazepine in the week before the PET scan [18F] DPA-714 given the potential consequences for TSPO receivers

  • Contraindications to MRI in patients with:

    1. Metallic foreign body eye.
    2. Any implanted electronic medical irremovably (pacemaker, neurostimulator, cochlear implants ...)
    3. Metal heart valve,
    4. Vascular clips formerly located on cranial aneurysm.
  • Treatment in the month before the PET scan [18F] DPA-714 antagonist N-methyl-D-aspartate (NMDA) (memantine)
  • Pregnant women, lactating women, and women in age for procreation and without reliable contraception or without history of hysterectomy
  • ◦Person under guardianship

Sites / Locations

  • University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

amyotrophic lateral sclerosis (ALS)

Arm Description

[18F]DPA-714 PET

Outcomes

Primary Outcome Measures

Concentration of cytokines in cerebrospinal fluid (pg/mL)

Secondary Outcome Measures

Fixation and distribution of [18F]DPA-714 (Binding Potential BP)

Full Information

First Posted
March 2, 2015
Last Updated
May 29, 2017
Sponsor
University Hospital, Tours
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1. Study Identification

Unique Protocol Identification Number
NCT02405403
Brief Title
Microglial Activation Role In ALS (MARIA)
Acronym
MARIA
Official Title
Microglial Activation Role In ALS (MARIA)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Withdrawn
Why Stopped
It was more difficult than planned to find patients filling inclusion criteria and those which corresponded didn't agree to participate
Study Start Date
March 2015 (Anticipated)
Primary Completion Date
September 2016 (Anticipated)
Study Completion Date
March 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Neuroinflammation, characterized in particular by microglia activation, is an essential component of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Translocator Protein (TSPO) is recognized as a specific and sensitive biomarker of neuroinflammation, reflecting disease activity. An experimental radiopharmaceutical specific of TSPO expression, namely [18F]DPA714, allow to quantify this microglial activation using Positon Emission Tomography (PET) imaging. The purpose of this study is to longitudinally correlate the spatial distribution of neuroinflammation with the pro- or anti-inflammatory state of activated microglia cells in ALS, in order to evaluate neurotoxic or neuroprotective microglia activity, by complementary approaches in 20 ALS patients: in vitro: measuring concentrations of several pro- and anti-inflammatory cytokines secreted by microglial cells in the cerebrospinal fluid (CSF). in vivo: [18F]DPA714 PET imaging. These assays will be performed in the framework of the clinical follow-up of ALS patients, at the diagnosis of ALS disease and 6 months latter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
amyotrophic lateral sclerosis disease, PET, microglial activation

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
amyotrophic lateral sclerosis (ALS)
Arm Type
Experimental
Arm Description
[18F]DPA-714 PET
Intervention Type
Drug
Intervention Name(s)
[18F]DPA-714 PET
Other Intervention Name(s)
[18F]DPA-714
Intervention Description
[18F]DPA-714 Positron Emission Tomography
Primary Outcome Measure Information:
Title
Concentration of cytokines in cerebrospinal fluid (pg/mL)
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Fixation and distribution of [18F]DPA-714 (Binding Potential BP)
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent Age ≥ 18 years old Patient with probable or definite sporadic Amyotrophic Lateral Sclerosis (ALS) form according to the modified criteria of El Escorial Treated with riluzole 2 weeks Evolution less than 18 months Mini-Mental State Examination (MMS) score ≥ 26 and Frontal Assessment Battery (FAB) (normal) Affiliated to a social security system Exclusion Criteria: Another unbalanced progressive pathology Vascular diseases (hypertension, diabetes, smoking, dyslipidemia) unbalanced Forced vital capacity <75% Weight loss> 10% of the weight before disease Status "low affinity binder" or "mixed affinity binder", the TSPO respect to the [18 F] DPA-714, which can interfere with the process of neuroinflammation: drugs with anti-inflammatory drugs (NSAIDs, corticosteroids, azathioprine, anti-tumor necrosis factor (TNF), antibiotics) Benzodiazepine in the week before the PET scan [18F] DPA-714 given the potential consequences for TSPO receivers Contraindications to MRI in patients with: Metallic foreign body eye. Any implanted electronic medical irremovably (pacemaker, neurostimulator, cochlear implants ...) Metal heart valve, Vascular clips formerly located on cranial aneurysm. Treatment in the month before the PET scan [18F] DPA-714 antagonist N-methyl-D-aspartate (NMDA) (memantine) Pregnant women, lactating women, and women in age for procreation and without reliable contraception or without history of hysterectomy ◦Person under guardianship
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe CORCIA, PhD
Organizational Affiliation
CHRU Tours
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
22539580
Citation
Corcia P, Valdmanis P, Millecamps S, Lionnet C, Blasco H, Mouzat K, Daoud H, Belzil V, Morales R, Pageot N, Danel-Brunaud V, Vandenberghe N, Pradat PF, Couratier P, Salachas F, Lumbroso S, Rouleau GA, Meininger V, Camu W. Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations. Neurology. 2012 May 8;78(19):1519-26. doi: 10.1212/WNL.0b013e3182553c88. Epub 2012 Apr 25.
Results Reference
result
PubMed Identifier
20949041
Citation
Blasco H, Corcia P, Moreau C, Veau S, Fournier C, Vourc'h P, Emond P, Gordon P, Pradat PF, Praline J, Devos D, Nadal-Desbarats L, Andres CR. 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS One. 2010 Oct 8;5(10):e13223. doi: 10.1371/journal.pone.0013223.
Results Reference
result
PubMed Identifier
22172392
Citation
Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL, Maia S, Corcia P, Stabin MG, Reynolds A, Kassiou M, Guilloteau D. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14.
Results Reference
result
PubMed Identifier
22274580
Citation
Corcia P, Ingre C, Blasco H, Press R, Praline J, Antar C, Veyrat-Durebex C, Guettard YO, Camu W, Andersen PM, Vourc'h P, Andres CR. Homozygous SMN2 deletion is a protective factor in the Swedish ALS population. Eur J Hum Genet. 2012 May;20(5):588-91. doi: 10.1038/ejhg.2011.255. Epub 2012 Jan 25.
Results Reference
result
PubMed Identifier
23300829
Citation
Corcia P, Tauber C, Vercoullie J, Arlicot N, Prunier C, Praline J, Nicolas G, Venel Y, Hommet C, Baulieu JL, Cottier JP, Roussel C, Kassiou M, Guilloteau D, Ribeiro MJ. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941. doi: 10.1371/journal.pone.0052941. Epub 2012 Dec 31.
Results Reference
result

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Microglial Activation Role In ALS (MARIA)

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