PET Imaging of the Translocator Proteine Ligands (TSPO) With [18 F] DPA-714 Biomarker of NeuroInflammation in Cognitive Decline (NIDECO)
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- University Hospital, Tours
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Fixation and distribution of [18F]DPA-714 (Binding Potential BP)
Study Overview
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.
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
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Criteria common to all participants:
- •Signed informed consent
- •Age ≥ 60 years old (60-80 years old)
- •Native language: French
- •Correct sensory abilities (hearing aids accepted) to perform the tests
- •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
- •contraindication for MRI
- •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
- •No inclusion criteria :
- •medical history of evolutive disease with conséquences on NCS, chronic alcohol intake, severe depression with MADRS stage > 18
- •MA subjects : antagonistic treatment with N-methyl-D-aspartate
- •MA or MCI subjects : anomaly on neurologic clinical examination different of the usual symptomatology
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: [18F]DPA-714 PET/ [18F]AV-45 PET/neuropsychological assessment (Drug)
Outcomes
Primary Outcomes
Fixation and distribution of [18F]DPA-714 (Binding Potential BP)
Time Frame: 2 years
[18F]AV-45 Standard Uptake Values ratio
Time Frame: 2 years
Secondary Outcomes
- Relationship between [18F]DPA-714 uptake and cognitive, affective symptoms at baseline.(2 years)