Microglial Activation Role In ALS (MARIA)

Early Phase 1

Withdrawn

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: [18F]DPA-714 PET

• Registration Number: NCT02405403
• Lead Sponsor: University Hospital, Tours

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-03-02
• Study First Submitted QC: 2015-03-27
• Study First Posted: 2015-04-01
• Primary Completion: 2016-09
• Study Completion: 2017-03
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-29
• Last Update Posted: 2017-05-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
amyotrophic lateral sclerosis (ALS)	[18F]DPA-714 PET	\[18F\]DPA-714 PET

Primary Outcome Measures

Name	Time	Method
Concentration of cytokines in cerebrospinal fluid (pg/mL)	18 months

Secondary Outcome Measures

Name	Time	Method
Fixation and distribution of [18F]DPA-714 (Binding Potential BP)	18 months

Trial Locations

Locations (1)

University Hospital; 🇫🇷 Tours, France