Precision Medicine in Alzheimer's Disease : Integration of Resilience Metrics and Risk Factors - Validation Cohort BioCogBank-AD

NCT ID: NCT06582199

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-31
• Study Completion Date: 2027-09-30

Brief Summary

BioCogBankAD aims at building a prospective clinical practice cohort of 244 patients with biologically confirmed mild cognitive impairment due to Alzheimer's Disease (AD) or mild AD in order to validate data regarding markers of resilience toward AD pathophysiological process discovered in an upstream project called AD-Resilience.

Detailed Description

Alzheimer's disease (AD) is a leading cause for individual and caregiver burden associated with neurodegenerative diseases (NDs) in an aging population, afflicting + 35 million people worldwide, and spiraling costs. Major advances have been made during the last 20 years in the understanding of AD pathophysiological process. It is now well demonstrated that the course of the disease extend over more than 20 years with long pre and pauci-symptomatic periods.

A major need and challenge in translational research on Alzheimer's disease (AD) is to predict disease progression rate and/or time to clinical conversion, notably in the early phases of the AD process, such as mild cognitive impairment (MCI). Current markers such as Aß and tau species measured in cerebrospinal fluid (CSF) can differentiate AD from control and are currently used in daily clinical practice to assess presence of AD pathological process in patients with cognitive complaints. However, they do not account for cellular compensation and resistance mechanisms, the so-called "resilience" process.

Consequently, both prediction of AD progression in single patients and personalized adaptation of management and treatment remain highly limited. Moreover, there is an important unmet need regarding targeted prevention.

AD-Resilience is a translational research study funded by Agence Nationale pour la Recherche (ANR) and Direction Générale de l'Organisation des Soins (DGOS) that aims at identifying and validating markers of the biological processes underlying the mechanisms of brain resilience toward AD pathological process. Using blood samples, the investigators will produce the molecular-profile data that are needed to assess the resilience and brain homeostasis status of patients facing the AD process. Results will be processed using high-end machine learning (ML) to overcome the limitations associated with sub-optimal reliability and precision of dimensional data analysis.

These biomarkers will be identified using data and samples from an already available nationwide research cohort (BALTAZAR). In order to ensure validity and facilitate transfer to clinical practice, results from this preliminary study will have to be confirmed in an independent, prospective cohort of patients reflecting the full spectrum and real-life heterogeneity of AD.

For this purpose, BioCogBankAD study aims at building this validation cohort. 244 patients with MCI or early dementia due to AD will be recruited in the present study and prospectively followed during three years. Blood samples (plasma, DNA and PaxGen) will be taken from these patients in order to measure the biomarkers previously identified in the exploratory study. Clinical follow-up including including standardized neuropsychological examination and blood sampling (plasma) will be performed annually.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Exploratory group

Group Type: EXPERIMENTAL

Blood sample

Intervention Type: OTHER

Plasma, DNA, RNA and PBMC Sampling

Neuropsychological battery tests

Intervention Type: BEHAVIORAL

• Short term memory: Digit span (forward and backward)
• Long term memory: Free and Cued selective reminding Test
• Language and semantic Memory : Verbal Fluency (Category and Litteral), Image Naming (DO 40)
• Praxis
• Visuo Spatial abilities: Rey-Osterrieth Complex Figure Test
• Attention and executive functions: Trail Making Test (TMT) Part A and B, Frontal Assessment Battery (FAB)
• Autonomy in daily life activities : Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL), Instrumental Activities of Daily Living (IADL)
• Mood and anxiety: Hospital Anxiety and Depression Scale (HADS)
• Cognitive reserve : Cognitive Reserve Index questionnaire (CRIq)

Interventions

Blood sample

Plasma, DNA, RNA and PBMC Sampling

Intervention Type: OTHER

Neuropsychological battery tests

• Short term memory: Digit span (forward and backward)
• Long term memory: Free and Cued selective reminding Test
• Language and semantic Memory : Verbal Fluency (Category and Litteral), Image Naming (DO 40)
• Praxis
• Visuo Spatial abilities: Rey-Osterrieth Complex Figure Test
• Attention and executive functions: Trail Making Test (TMT) Part A and B, Frontal Assessment Battery (FAB)
• Autonomy in daily life activities : Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL), Instrumental Activities of Daily Living (IADL)
• Mood and anxiety: Hospital Anxiety and Depression Scale (HADS)
• Cognitive reserve : Cognitive Reserve Index questionnaire (CRIq)

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Diagnosis of AD according to IWG-2 2014 criteria
• Age 50-90 year old
• Affiliated or beneficiary of a social security scheme
• MMSE ≥ 20
• Abnormal CSF Aβ42 or Aβ40/Aβ42 ratio according to local cut-offs
• Abnormal CSF phosphorylated and total Tau according to local cut-offs
• Ability to pass neuropsychological assessments
• Availability of a brain MRI with T1 volumetric sequence performed within 1 year

Exclusion Criteria

• Other cause of dementia
• Participation in an AD therapeutic clinical trial
• Protected adults (including individual under guardianship by court order),

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Agency, France

OTHER

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Centre National de la Recherche Scientifique, France

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel GOGNAT, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Christian NERRI, PhD

Role: STUDY_CHAIR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Hôpital Cochin

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Olivier HANON, MD, PhD

Role: CONTACT

olivier.hanon@aphp.fr

+ 1 44 08 33 81

Valérie PLENCE, MSc

Role: CONTACT

valerie.plence@aphp.fr

+33 1 54 41 11 78

Facility Contacts

Olivier HANON, MD, PhD

Role: primary

olivier.hanon@aphp.fr

+33 1 44 08 33 81

Other Identifiers

2024-A00457-40

Identifier Type: OTHER

Identifier Source: secondary_id

APHP210991

Identifier Type: -

Identifier Source: org_study_id