Investigation of AlzHeimer's Predictors in Subjective Memory Complainers - Extension Study (INSIGHT-2)

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Memory Disorders; Memory Complaint
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadjia YOUNSI; Phone Number: +331 42 16 75 15; Email: nadjia.younsi@icm-institute.org

Study Locations

• France
  • Ile de france
    • Paris, Ile de france, France, 75013
      • Recruiting
      • Hopital Pitie Salpetriere
      • Contact: Stéphanie Bombois; Phone Number: +33142167515; Email: stephanie.bombois@aphp.fr
      • Contact: Nadjia YOUNSI; Phone Number: +33142167515; Email: nadjia.younsi@icm-institute.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 95 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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®).
• Participation in any clinical trial of an investigational product in the last 30 days before the screening (during all study duration co-inclusion in other clinical trial of an investigational product or observational research [biomarker cohort e.g.] will be possible but the information would need to be recorded).
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: All participants

Procedure: Electroencephalogram (EEG); 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.; Procedure: Oculomotor tests; All participants in the INSIGHT-2 study are invited to perform the oculomotor test, excepting subjects reporting oculomotor disorders.; Procedure: MRI; All INSIGHT-2 participants will undergo a baseline MRI (structural and resting state fMRI) a follow-up MRI at M12, M36 and M60.; Radiation: 18-F amyloid PET Scan; 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.; Radiation: 18F-fluorodeoxyglucose (FDG) PET Scan; 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.; Biological: Blood sampling; 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.; Biological: Lumbar puncture; A lumbar puncture for cerebrospinal fluid (CSF) collection is proposed to all participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline	CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72	Each 1 year from baseline for 5 years (M60)
Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline	Exploratory outcomes	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)	Exploratory outcomes	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)	Exploratory outcomes	Each 1 year from baseline for 5 years (M60)
Conversion to symptomatic non-AD cognitive disease	Atypical AD according to IWG 2014 criteria	Each 1 year from baseline for 5 years (M60)
Diagnosis of cerebral amyloid angiopathy based on V2.0 BOSTON criteria	As described in the following reference: Charidimou et al., Lancet Neurol. 2022 Aug;21(8):714-725	Each 1 year from baseline for 5 years (M60)

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Stéphanie BOMBOIS, MD, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A)

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2023
• Primary Completion (Estimated): October 9, 2030
• Study Completion (Estimated): October 9, 2030

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: neurology; risks factors; memory complaint; brain amyloid load; neurosciences; memory disorders
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Memory Disorders; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: C20-70

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No