NCT01775696

Brief Summary

The main objective of this study is to investigate the central and peripheral inflammatory, as well as the spontaneous Aβ-specific, immune responses at the asymptomatic stage and early stages of AD by combining molecular imaging techniques with blood biomarker analyses. The early and preclinical stages of AD will be studied in the relatives of patients with PSEN1, PSEN2 or APP mutations that are at-risk (50%) to be mutation carriers. This study will evaluate the contribution of Inflammatory and immune anti-Aβ responses (I2ARs) in AD progression. Inclusion of sporadic and familial forms of AD will aid in studying the chronology of pathological events. Clinical follow-ups will be conducted annually for two years and will include an MRI and a blood draw on the last visit. We expect I2ARs to appear in the early stages of the disease and to constitute new prognostic factors. I2ARs could also become therapeutic markers for the assessment of novel anti-amyloid treatments and may offer new insights to the development of Aβ-specific immunotherapy strategies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Dec 2011

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 8, 2011

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

January 23, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 25, 2013

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 4, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 4, 2017

Completed
Last Updated

November 6, 2017

Status Verified

November 1, 2017

Enrollment Period

5.3 years

First QC Date

January 23, 2013

Last Update Submit

November 3, 2017

Conditions

Alzheimer's Disease

Keywords

Alzheimer's diseasePittsburgh binding Compound (PiB)Positron Emission Tomography (PET)InflammationAnti Abeta immune responsesBlood markersMRI

Outcome Measures

Primary Outcomes (1)

  • evolution of blood markers

    I2AR measures \[Time Frame: at 0, 12 months and 24 months\]

    from 0 to 24 months

Secondary Outcomes (2)

  • Patient's blood cell modification assessment

    from M0 to M24

  • [F18] DPA-714 PET examination

    Month 3

Other Outcomes (6)

  • Analysis of prognostic value of I2AR measures on clinical measures

    12 months

  • Analysis of prognostic value of I2AR measures on clinical measures

    24 months

  • Analysis of prognostic value of I2AR measures on neuropsychological measures

    12 months

  • +3 more other outcomes

Study Arms (5)

sporadic AD

80 sporadic AD patients (40 at the stage of MCI, 40 at the stage of mild or moderate dementia)

familial forms of AD

15 familial forms of AD caused by APP, PSEN1 or PSEN2 mutations

asymptomatic relatives

30 asymptomatic relatives to familial AD patients

controls

40 controls

genetic FTD

5 genetic forms of FTD

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

80 sporadic AD patients (40 at the stage of MCI, 40 at the stage of mild or moderate dementia), 15 familial forms of AD caused by APP, PSEN1 or PSEN2 mutations, 30 asymptomatic relatives to familial AD patients, 40 controls, 5 genetic forms of FTD

You may qualify if:

  • Sporadic AD patients at a prodromal stage:
  • Be older than 30 years old.
  • Progressive amnestic syndrome of the hippocampal type, defined by a free recall score
  • ≤ 18 and a total recall score ≤ 40 on the Free and Cued Selective Recall Reminding Test (FCSRT).
  • Absence of overt dementia.
  • CDR (Clinical Dementia Rating Scale) = 0.5.
  • No impact on activities of daily living, or only one item impaired at the first level of the Instrumental Activity of Daily Living Scale.
  • Absence of general or systemic disorders that may interfere with cognition.
  • Absence of brain lesions as determined by MRI that may account for part of the clinical presentation.
  • Sporadic AD patients at a mild to moderate dementia stage:
  • Be older than 30 years old.
  • NINCDS-AIREN criteria.
  • CDR (Clinical Dementia Rating Scale) = 1 or 2
  • Normal controls :
  • Be older than 30 years old.
  • +11 more criteria

You may not qualify if:

  • Psychiatric disorder or major depression
  • Contraindication for MRI examination : carrying a cardiac pacemaker, any ferromagnetic metallic implants or foreign bodies (an internal electrical or magnetic device, a valvular prosthesis), claustrophobic subject
  • Alcoholism
  • Vascular lesions on MRI
  • Allergy either to PiB or to DPA
  • Non health insurance affiliation
  • Pregnant women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

APHP - Pitié Salpetriere Hospital

Paris, 75013, France

Location

Related Publications (4)

  • Corlier F, Rivals I, Lagarde J, Hamelin L, Corne H, Dauphinot L, Ando K, Cossec JC, Fontaine G, Dorothee G, Malaplate-Armand C, Olivier JL, Dubois B, Bottlaender M, Duyckaerts C, Sarazin M, Potier MC; Clinical ImaBio3 Team. Modifications of the endosomal compartment in peripheral blood mononuclear cells and fibroblasts from Alzheimer's disease patients. Transl Psychiatry. 2015 Jul 7;5(7):e595. doi: 10.1038/tp.2015.87.

    PMID: 26151923RESULT

  • Hamelin L, Bertoux M, Bottlaender M, Corne H, Lagarde J, Hahn V, Mangin JF, Dubois B, Chupin M, de Souza LC, Colliot O, Sarazin M. Sulcal morphology as a new imaging marker for the diagnosis of early onset Alzheimer's disease. Neurobiol Aging. 2015 Nov;36(11):2932-2939. doi: 10.1016/j.neurobiolaging.2015.04.019. Epub 2015 Jul 15.

    PMID: 26256787RESULT

  • Hamelin L, Lagarde J, Dorothee G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, Dubois B, Gervais P, Colliot O, Potier MC, Bottlaender M, Sarazin M; Clinical IMABio3 team. Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016 Apr;139(Pt 4):1252-64. doi: 10.1093/brain/aww017. Epub 2016 Mar 15.

    PMID: 26984188RESULT

  • Peyronneau MA, Kuhnast B, Nguyen DL, Jego B, Sayet G, Caille F, Lavisse S, Gervais P, Stankoff B, Sarazin M, Remy P, Bouilleret V, Leroy C, Bottlaender M. [18F]DPA-714: Effect of co-medications, age, sex, BMI and TSPO polymorphism on the human plasma input function. Eur J Nucl Med Mol Imaging. 2023 Sep;50(11):3251-3264. doi: 10.1007/s00259-023-06286-1. Epub 2023 Jun 9.

    PMID: 37291448DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood

MeSH Terms

Conditions

Alzheimer DiseaseInflammation

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental DisordersPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Marie Sarazin, MD, PhD

    APHP

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 23, 2013

First Posted

January 25, 2013

Study Start

December 8, 2011

Primary Completion

April 4, 2017

Study Completion

April 4, 2017

Last Updated

November 6, 2017

Record last verified: 2017-11

Locations

FR(1)