NIDeCo: PET Imaging of the Translocator Proteine Ligands (TSPO) With [18 F] DPA-714 Biomarker of NeuroInflammation in Cognitive Decline (NIDECO)
Study Details
Study Description
Brief Summary
Alzheimer's disease (AD) is the most common cause of dementia in elderly subjects. AD is characterized by brain lesions like extracellular deposits of ß-amyloïd proteins in senile plaques and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein, both of which are associated with the loss of neurons. The development of disease biomarkers for AD (Tau, PhTau and βamyloid dosing in the cerebrospinal fluid, brain MRI, amyloid PET imaging and fluorodeoxyglucose PET imaging) to identify the pathophysiological processes underlying cognitive impairment biomarkers, have been incorporated into revised diagnosis guidelines.
Post-mortem human AD and AD animal model studies have reported inflammatory processes also implicated in the neuropathology of AD, and upregulated levels of pro-inflammatory cytokines.
In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands (tracers) for use with positron emission tomography (PET). The translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR), a receptor located in the outer membrane of mitochondria, is upregulated during neuroinflammation. So targeting TSPO with radiolabeled ligands for PET is considered as an attractive biomarker for neuroinflammation.
The main aim of this pilot study is to quantify neuroinflammation, in terms of fixation and distribution of [18F] DPA-714(Binding Potential BP), and to study its relationship with amyloid load, measured with in [18F]AV-45 (Standard Uptake Values ratio) in cognitive decline.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Molecular imaging of microglial activation could help us document the central inflammatory status of study subjects and assist us in designing future research studies particularly with respect to which subjects to enrol into clinical trials and to evaluate the benefit of specific therapies in selected groups, for example, by monitoring the effects of Aß immunization.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Memory complaint /MCI/ mild to moderate MA Memory complaint (without cognitive decline): 12 patients/ Mild Cognitive Impairment: 12 patients/ Mild to moderate Alzheimer Disease: 12 patients |
Drug: [18F]DPA-714 PET/ [18F]AV-45 PET/neuropsychological assessment
|
Outcome Measures
Primary Outcome Measures
- Fixation and distribution of [18F]DPA-714 (Binding Potential BP) [2 years]
- [18F]AV-45 Standard Uptake Values ratio [2 years]
Secondary Outcome Measures
- Relationship between [18F]DPA-714 uptake and cognitive, affective symptoms at baseline. [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
Criteria common to all participants:
-
Signed informed consent
-
Age ≥ 60 years old (60-80 years old)
-
Native language: French
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Correct sensory abilities (hearing aids accepted) to perform the tests
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Affiliated to a social security system
Criteria for patients with mild to moderate Alzheimer disease defined according to the
NINCDS-ADRDA {McKhann, 2011 # 408}:
- MMS between 20 and 25
Criteria for amnestic MCI patients:
- Amnestic mildcognitive disorder evoking a MA in pre stage dementia {Dubois, 2010 # 273, Dubois, 2007 # 42; Pertersen, 1999 # 21, Albert, 2011 # 409} older than 60 years.
Criteria for patients with isolated memory Complaint (Without Cognitive Decline):
-
MMS score ≥ 26
-
Normal performance by age and educational level
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital of Tours | Tours | France | 37000 |
Sponsors and Collaborators
- University Hospital, Tours
Investigators
- Principal Investigator: Caroline HOMMET, PhD, University Hospital of Tours (CMRR)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PHAO13-CH/ NIDeCo