Central and Systemic Inflammation in Alzheimer's Disease (IMABio3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01775696
First received: January 23, 2013
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition
Alzheimer's Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of Central and Systemic Inflammation and Aβ-specific Immune Responses in Early AD

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • evolution of blood markers [ Time Frame: from 0 to 24 months ] [ Designated as safety issue: No ]
    I2AR measures [Time Frame: at 0, 12 months and 24 months]


Secondary Outcome Measures:
  • Patient's blood cell modification assessment [ Time Frame: from M0 to M24 ] [ Designated as safety issue: No ]
    Patient's blood cell modification assessment [ Time Frame: at 0, 12 months and 24 months ]

  • [F18] DPA-714 PET examination [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
    • [F18] DPA-714 PET examination
    • Relationship between PIB examination and I2AR measures
    • Relationship between PIB examination and DPA PET examination


Other Outcome Measures:
  • Analysis of prognostic value of I2AR measures on clinical measures [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Analysis of prognostic value of I2AR measures on clinical measures [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Analysis of prognostic value of I2AR measures on neuropsychological measures [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Analysis of prognostic value of I2AR measures on neuropsychological measures [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Analysis of prognostic value of I2AR measures on hippocampal volumes [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Analysis of prognostic value of I2AR measures on hippocampal volumes [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood


Estimated Enrollment: 170
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-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

Criteria

Inclusion criteria :

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.
  • An absence of psychiatric disorder
  • An absence of subjective problems with memory and normal scores on the Mini Mental State Examination (MMSE ≥ 27)

Familial symptomatic AD patients with PSEN1, PSEN2 or APP mutations:

  • Be older than 18 years old.
  • Patients will be identified by the team of neurogeneticists

Relatives at 50% risk of familial AD:

  • These subjects will be recruited from families affected with autosomal dominant AD that is due to the mutation of the PSEN1, PSEN2 or APP genes. In these families, the first-degree relatives of patients with a mutation have a 50% risk of having the mutation that was identified in the family.

Familial frontotemporal dementia (FTD) patients :

  • FTD patients with mutations in the progranulin gene or MAPT (tau) gene will be identified by the team of neurogeneticists at Rouen and Paris (Salpetriere). Familial FTD patients with known pathologies will be included regardless of the severity of the disease, given the small number of patients involved.

Concomitant therapy :

  • All subjects will be asked about their history of benzodiazepine treatment: flunitrazepam, triazolam, and diazepam, which have a moderate affinity for PBR, will be forbidden or will be stopped before inclusion. Clonazepam, lorazepam, zolpidem, and zopiclone, which have a very low affinity for PBR, will be allowed. For all other benzodiazepines, specific research on their affinity toward PBR will be performed before definitive inclusion.

Subjects taking acetylcholinesterase inhibitor or memantine will be admitted.

Exclusion criteria :

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01775696

Contacts
Contact: Marie Sarazin, MD, PhD marie.sarazin@psl.aphp.fr

Locations
France
APHP - Pitié Salpetriere Hospital Recruiting
Paris, France, 75013
Contact: Marie Sarazin, MD, PhD    + 33 1 42 16 75 25    marie.sarazin@psl.aphp.fr   
Principal Investigator: Marie Sarazin, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Marie Sarazin, MD, PhD APHP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01775696     History of Changes
Other Study ID Numbers: P100145
Study First Received: January 23, 2013
Last Updated: June 13, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Alzheimer's disease
Pittsburgh binding Compound (PiB)
Positron Emission Tomography (PET)
Inflammation
Anti Abeta immune responses
Blood markers
MRI

Additional relevant MeSH terms:
Alzheimer Disease
Inflammation
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014