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NCT Number: NCT05806697

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

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.

Recruiting

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Key information

Age range

70 year–95 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

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.

Oculomotor tests

Procedure

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

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.

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.

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.

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.

Lumbar puncture

Biological

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

Primary outcomes

  1. 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)

    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

Secondary outcomes

  1. 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)

    CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72

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

    Time frame: Each 1 year from baseline for 5 years (M60)

    Exploratory outcomes

  3. 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)

    Exploratory outcomes

  4. 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)

    Exploratory outcomes

  5. Conversion to symptomatic non-AD cognitive disease

    Time frame: Each 1 year from baseline for 5 years (M60)

    Atypical AD according to IWG 2014 criteria

  6. Diagnosis of cerebral amyloid angiopathy based on V2.0 BOSTON criteria

    Time frame: Each 1 year from baseline for 5 years (M60)

    As described in the following reference: Charidimou et al., Lancet Neurol. 2022 Aug;21(8):714-725

Study contacts

Contact information is provided by the study sponsor or research team.

Nadjia YOUNSI

CONTACT

[email protected]

+331 42 16 75 15

Sponsors and collaborators

Lead sponsor

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

Other Gov

Registry information

Acronym: INSIGHT-2

Important dates

Study start
2023
Primary completion
2030
Study completion
2030
First posted
Apr 10, 2023
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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