Clinical trial NCT02405403: Microglial Activation Role In ALS (MARIA)
Official title: Microglial Activation Role In ALS (MARIA)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis disease
PET
microglial activation
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2015-04-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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:

  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

Primary outcomes:
measure: Concentration of cytokines in cerebrospinal fluid (pg/mL)
timeFrame: 18 months
Secondary outcomes:
measure: Fixation and distribution of [18F]DPA-714 (Binding Potential BP)
timeFrame: 18 months
Other outcomes:
Locations:
city: Tours
country: France
facility: University Hospital
Study officials:
affiliation: CHRU TOURS
name: Philippe CORCIA, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.