Investigation of AlzHeimer's Predictors in Subjective Memory Complainers - Extension Study

NCT05806697 | Recruiting

• 1 other identifier: C20-70
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

A regional, single-center, prospective, observational academic cohort will follow subjects who previously participated in the INSIGHT study and who agree an extension of their follow-up in the INSIGHT-2 research for additional 5-6 years. An annual multimodal evaluation (cognitive, oculomotor, biological and neuroimaging) will be proposed in order to describe the natural history of preclinical Alzheimer's disease (AD). The primary endpoint is the conversion to the symptomatic stage in subjects at risk, identified by positive amyloid staining (A+) on florbetapir positron emission tomography (PET) imaging. The size of the cohort is estimated to around 240 participants (61 A+ subjects) among the 318 participants included in the main cohort (88 A+ subjects). The follow-up in the INSIGHT-2 cohort will be lightened compared to that of the main cohort with an annual frequency of visits rather than a six-monthly one.

Conditions

Alzheimer Disease; Memory Complaint; Memory Disorders

Keywords

risks factors; brain amyloid load; neurosciences; neurology; memory complaint; memory disorders

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the conversion to typical AD during the 5-year follow-up.

  Typical AD according to International Working Group (IWG) 2014 criteria = amyloid-positive participants, with an abnormal decline of episodic memory performance on the Free and Cued Selective Reminding Test

  every year through study completion, from baseline for 5 years (M60)

Secondary Outcomes (6)

• Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline

  Each 1 year from baseline for 5 years (M60)

• Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline

  Each 1 year from baseline for 5 years (M60)

• Change of the score in different self-administered, informant based questionnaires (including the Quality Of Life (QOL), Ascertain Dementia 8 (AD)8 Dementia Screening Interview, Aging Brain Care Monitor)

  Each 1 year from baseline for 5 years (M60)

• Rate of change in biomarkers measured from blood, CSF, structural and functional neuroimaging (MRI), EEG and molecular neuroimaging (18F-FDG-PET and amyloid imaging)

  Each 1 year from baseline for 5 years (M60)

• Conversion to symptomatic non-AD cognitive disease

  Each 1 year from baseline for 5 years (M60)

Study Arms (1)

All participants

OTHER

Procedure: Electroencephalogram (EEG); Procedure: Oculomotor tests; Procedure: MRI; Radiation: 18-F amyloid PET Scan; Radiation: 18F-fluorodeoxyglucose (FDG) PET Scan; Biological: Blood sampling; Biological: Lumbar puncture

Interventions

Electroencephalogram (EEG) PROCEDURE

The EEG will be uniquely performed during for the whole study if a given subject converts to symptomatic AD or in the occurrence of significant cognitive decline.

All participants

Oculomotor tests PROCEDURE

All participants in the INSIGHT-2 study are invited to perform the oculomotor test, excepting subjects reporting oculomotor disorders.

All participants

MRI PROCEDURE

All INSIGHT-2 participants will undergo a baseline MRI (structural and resting state fMRI) a follow-up MRI at M12, M36 and M60.

All participants

18-F amyloid PET Scan RADIATION

The primary endpoint is conversion to the symptomatic stage in subjects at risk, identified by positive amyloid staining (A+) on florbetapir PET imaging. Participants will receive an injection of 18F-Florbetapir prior to undergoing amyloid PET scanning. Florbetapir (18F) is an experimental imaging compound labeled with \[18F\] fluorine that decays by positron (β+) emission and has a half-life of 109.77 min. This procedure will be done at baseline.

All participants

18F-fluorodeoxyglucose (FDG) PET Scan RADIATION

Participants will receive an injection of Fludeoxyglucose 18F prior to undergoing FDG-PET. The \[18F\]FDG is the most well-known radiopharmaceutical positron emitter, in both clinical and preclinical fields.

All participants

Blood sampling BIOLOGICAL

A total of 80 ml of whole blood will be collected for each participant in the INSIGHT-2 study for routine laboratory assessment and biobank sampling.

All participants

Lumbar puncture BIOLOGICAL

A lumbar puncture for cerebrospinal fluid (CSF) collection is proposed to all participants.

All participants

Eligibility Criteria

• Age: 70 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subjects that previously participated in the INSIGHT cohort
• Aged 70 to 95 years old
• Having signed an informed consent
• Willing to and able undergo a baseline PET amyloid imaging
• Affiliating to the French health-care system
• Having an identified informant who has sufficient contact with the participant and has to be able to provide accurate information, at least by phone, about the participants' cognitive and functional abilities.

You may not qualify if:

• Clinical Dementia Rating ≥1 at screening/baseline visit only
• Fulfilling research diagnostic criteria for any type of dementia-related disorder at screening visit (clinical AD, Dementia with Lewy Bodies \[DLB\], fronto-temporal dementia \[FTD\], vascular dementia, chronic traumatic encephalopathy \[CTE\], Limbic-predominant Age-related TDP-43 Encephalopathy \[LATE\], Primary age-related tauopathy \[PART)
• Presence of any medical condition associated with a long-term risk of cognitive impairment or dementia including Parkinson's disease, brain tumor, subdural hematoma, vascular malformations, territorial stroke (excluding smaller watershed strokes), chronic hydrocephalus, traumatic brain injury with neurological sequelae, active alcohol/drug abuse, major depressive disorder, schizophrenia and bipolar disorder
• Current serious or unstable illnesses (including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic or hematologic disease) that might make the subject's participation in an investigational trial unsafe
• Any contraindications for MRI/ PET scan procedure (claustrophobia, ferromagnetic object in the body), to FDG or to 18F-Florbetapir (Amyvid®).
• Hypersensitivity to the active substance or to any of the excipients of 18F-Florbetapir (Amyvid®).
• Unable to comply with protocol requirements in the opinion of the investigator
• Being under guardianship (safeguard of justice, curatorship or guardianship)
• Residence in skilled nursing facility, including nursing homes (EHPAD).

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Hôpital Pitié Salpêtrière

Paris, Île-de-France Region, 75013, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Memory Disorders

Interventions

Fluorodeoxyglucose F18; Magnetic Resonance Spectroscopy; Blood Specimen Collection; Spinal Puncture

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Biopsy; Diagnostic Techniques, Neurological; Therapeutics

Study Officials

• Stéphanie BOMBOIS, MD

  Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nadjia YOUNSI

CONTACT

+331 42 16 75 15; nadjia.younsi@icm-institute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: April 10, 2023
• Study Start: April 14, 2023
• Primary Completion (Estimated): October 9, 2030
• Study Completion (Estimated): October 9, 2030
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)