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

Overview

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.

Interventions

• 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.

Primary outcome measures

• The primary endpoint is the conversion to typical AD during the 5-year follow-up. [Time frame: every year through study completion, from baseline for 5 years (M60)]

Secondary outcome measures (6)

• Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline [Time frame: Each 1 year from baseline for 5 years (M60)]
• Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline [Time frame: 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) [Time frame: 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) [Time frame: Each 1 year from baseline for 5 years (M60)]
• Conversion to symptomatic non-AD cognitive disease [Time frame: Each 1 year from baseline for 5 years (M60)]
• Diagnosis of cerebral amyloid angiopathy based on V2.0 BOSTON criteria [Time frame: Each 1 year from baseline for 5 years (M60)]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Hôpital Pitié Salpêtrière — Paris

Identifiers

NCT: NCT05806697 · C20-70

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗