Microglial Activation Role In ALS (MARIA)

Regional University Hospital Center (CHRU)

Status and phase

Withdrawn

Early Phase 1

Conditions

Amyotrophic Lateral Sclerosis

Treatments

Drug: [18F]DPA-714 PET

Study type

Interventional

Funder types

Other

Identifiers

NCT02405403

PHAO-13-PC/MARIA

Details and patient eligibility

About

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.

Sex

All

Ages

18+ years old

Volunteers

No 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