Microglial Activation Role In ALS (MARIA)

Amyotrophic Lateral Sclerosis Clinical Trial

— MARIA  

Official title:

Microglial Activation Role In ALS (MARIA)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02405403
• Other study ID #: PHAO-13-PC/MARIA
• Status: Withdrawn
• Phase: Early Phase 1
• First received: March 2, 2015
• Last updated: May 29, 2017
• Start date: March 2015
• Est. completion date: March 2017

Study information

• Verified date: May 2017
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• [18F]DPA-714 PET
[18F]DPA-714 Positron Emission Tomography

Locations

Country	Name	City	State
France	University Hospital	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

References & Publications (5)

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. 20 — View 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):e1322 — View 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: — View 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. — View 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 i — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of cytokines in cerebrospinal fluid (pg/mL)		18 months
Secondary	Fixation and distribution of [18F]DPA-714 (Binding Potential BP)		18 months