Microglial Activation Role In ALS (MARIA)

• Status: Withdrawn
• Trial end date: 2017-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Tours

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