PET Imaging of the Translocator Proteine Ligands (TSPO) With [18 F] DPA-714 Biomarker of NeuroInflammation in Cognitive Decline (NIDECO)

NCT02062099 | Completed Phase 1 DMC

• 1 other identifier: PHAO13-CH/ NIDeCo
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Memory Complaint; Mild Cognitive Impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Fixation and distribution of [18F]DPA-714 (Binding Potential BP)

  2 years

• [18F]AV-45 Standard Uptake Values ratio

  2 years

Secondary Outcomes (1)

• Relationship between [18F]DPA-714 uptake and cognitive, affective symptoms at baseline.

  2 years

Study Arms (1)

Memory complaint /MCI/ mild to moderate MA

EXPERIMENTAL

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

Interventions

[18F]DPA-714 PET/ [18F]AV-45 PET/neuropsychological assessment DRUG

Memory complaint /MCI/ mild to moderate MA

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• medical history of evolutive disease with conséquences on NCS, chronic alcohol intake, severe depression with MADRS stage \> 18

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

University Hospital of Tours

Tours, 37000, France

Location

Related 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. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14.

  PMID: 22172392 RESULT

• Camus V, Payoux P, Barre L, Desgranges B, Voisin T, Tauber C, La Joie R, Tafani M, Hommet C, Chetelat G, Mondon K, de La Sayette V, Cottier JP, Beaufils E, Ribeiro MJ, Gissot V, Vierron E, Vercouillie J, Vellas B, Eustache F, Guilloteau D. Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging. 2012 Apr;39(4):621-31. doi: 10.1007/s00259-011-2021-8. Epub 2012 Jan 18.

  PMID: 22252372 RESULT

• La Joie R, Perrotin A, Barre L, Hommet C, Mezenge F, Ibazizene M, Camus V, Abbas A, Landeau B, Guilloteau D, de La Sayette V, Eustache F, Desgranges B, Chetelat G. Region-specific hierarchy between atrophy, hypometabolism, and beta-amyloid (Abeta) load in Alzheimer's disease dementia. J Neurosci. 2012 Nov 14;32(46):16265-73. doi: 10.1523/JNEUROSCI.2170-12.2012.

  PMID: 23152610 RESULT

• Beaufils E, Dufour-Rainfray D, Hommet C, Brault F, Cottier JP, Ribeiro MJ, Mondon K, Guilloteau D. Confirmation of the amyloidogenic process in posterior cortical atrophy: value of the Abeta42/Abeta40 ratio. J Alzheimers Dis. 2013;33(3):775-80. doi: 10.3233/JAD-2012-121267.

  PMID: 22986776 RESULT

• 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. 2012;7(12):e52941. doi: 10.1371/journal.pone.0052941. Epub 2012 Dec 31.

  PMID: 23300829 RESULT

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Emilie BEAUFILS, PhD

  University Hospital of Tours (CMRR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2014
• First Posted: February 13, 2014
• Study Start: January 1, 2014
• Primary Completion: May 22, 2018
• Study Completion: May 22, 2018
• Last Updated: September 14, 2022

Record last verified: 2014-02

Locations

FR (1)