Microglial Activation Role In ALS (MARIA)
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Withdrawn
- Sponsor
- University Hospital, Tours
- Locations
- 1
- Primary Endpoint
- Concentration of cytokines in cerebrospinal fluid (pg/mL)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
amyotrophic lateral sclerosis (ALS)
[18F]DPA-714 PET
Intervention: [18F]DPA-714 PET (Drug)
Outcomes
Primary Outcomes
Concentration of cytokines in cerebrospinal fluid (pg/mL)
Time Frame: 18 months
Secondary Outcomes
- Fixation and distribution of [18F]DPA-714 (Binding Potential BP)(18 months)