Clinical trial NCT02377206: Neuroinflammation and Cognitive Decline in Alzheimer Disease
Official title: Neuroinflammation and Cognitive Decline in Alzheimer Disease (AD) : Pilot Study of Translocator Proteins Ligand PET Imaging With [18F]DPA-714
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Alzheimer Disease
Keywords: PET
[18F]DPA-714
cognitive decline
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2015-03-03
Enrollment: 24
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the level of neuroinflammation in Alzheimer Disease subject (mild to moderate) estimated with Binding Potential (BP) of \[18F\]DPA-714, and its relationship with the kinetics of cognitive decline over a 24-month follow-up period (as assessed by Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) scores).

Detailed description: The purpose of this study is to assess the level of neuroinflammation in Alzheimer Disease subject (mild to moderate) estimated with Binding Potential (BP) of \[18F\]DPA-714 , and its relationship with the kinetics of cognitive decline over a 24-month follow-up period (as assessed by ADAS-Cog and MMSE scores).

(DPA-714 : N,N-diethyl-2-\[4-(2-fluoroethoxy)phenyl\]-5,7-dimethylpyrazolo\[1,5-a\]pyrimidine-3-acetamide)

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Age more than 50 years (included)
* necessary knowledge of French (write and oral) to do neuropsychological tests
* Study level upper (or equal) than 7 years (considering first year of grammar-school as start)
* People with Alzheimer Disease defined as National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA) standards : Light to mild AD defined by Mini-Mental State Examination (MMSE) score between 15 and 25 (included)
* Social security affiliation.

Exclusion Criteria:

* MMSE score lower than 15 and upper or equal to 26
* Evolutive disease which could possibly had consequences on central nervous system
* Inflammatory disease or evolutive neoplasia and/or C reactive protein (CRP) upper than 10mg/L
* Chronic use of alchohol and/or drug
* Serious depression defined by Montgomery Asberg Depression Rating Scale (MADRS) score higher than 18
* Surgical or medical condition in the last 3 months
* Long term treatment which could possibly interfere with inflammatory process (especially the month before PET \[18F\]DPA-714 imaging).
* Treatment by N-Methyl-D-Aspartate antagonist
* Treatment by Minocycline
* Treatment by benzodiazepine (especially the month before PET \[18F\]DPA-714 imaging) (Zolpidem, zopiclone and loprazolam excepted)
* Anomaly at neurological examination which is not a classical symptom
* Contraindication to magnetic resonance imaging (RMI)
* Florbetapir\[18F\] hypersensibility
* Participation to an other experimental protocol with drug.
* people under guardianship

Primary outcomes:
measure: Compare the neuroinflammation measured by fixing and layout of [18F]DPA-714 between 3 groups of patients : subjects suffering from Alzheimer disease light to mild stage, amnesiac MCI and patients suffering from isolated cognitive complaint
timeFrame: inclusion and 24 months
Secondary outcomes:
measure: Relationship passessment between [18F]DPA-714 fixing
timeFrame: Inclusion and 34 months
Other outcomes:
Locations:
city: Nantes
country: France
facility: university hospital of Nantes
city: Rennes
country: France
facility: University Hospital of Rennes
city: Tours
country: France
facility: University Hospital of Tours
Study officials:
affiliation: University Hospital of Tours
name: Vincent CAMUS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt C, Wolff M, Weitz M, Bartlau T, Korth C, Zerr I. Rapidly progressive Alzheimer disease. Arch Neurol. 2011 Sep;68(9):1124-30. doi: 10.1001/archneurol.2011.189.
citation: Soto ME, Andrieu S, Arbus C, Ceccaldi M, Couratier P, Dantoine T, Dartigues JF, Gillette-Guyonnet S, Nourhashemi F, Ousset PJ, Poncet M, Portet F, Touchon J, Vellas B. Rapid cognitive decline in Alzheimer's disease. Consensus paper. J Nutr Health Aging. 2008 Dec;12(10):703-13. doi: 10.1007/BF03028618.
citation: Helmer C, Andrieu S, Peres K, Orgogozo JM, Vellas B, Dartigues JF; REAL.fr Group. Predictive value of 6-month decline in ADAS-cog for survival without severe Alzheimer's disease. Dement Geriatr Cogn Disord. 2007;23(3):168-74. doi: 10.1159/000098516. Epub 2007 Jan 11.
citation: Lo RY, Jagust WJ; Alzheimer's Disease Neuroimaging Initiative. Vascular burden and Alzheimer disease pathologic progression. Neurology. 2012 Sep 25;79(13):1349-55. doi: 10.1212/WNL.0b013e31826c1b9d. Epub 2012 Sep 12.