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

Primary Purpose

Alzheimer Disease, Memory Complaint, Memory Disorders

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Electroencephalogram (EEG)
Oculomotor tests
MRI
18-F amyloid PET Scan
18F-fluorodeoxyglucose (FDG) PET Scan
Blood sampling
Lumbar puncture
Sponsored by
Institut National de la Santé Et de la Recherche Médicale, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alzheimer Disease focused on measuring risks factors, brain amyloid load, neurosciences, neurology, memory complaint, memory disorders

Eligibility Criteria

70 Years - 95 Years (Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Hôpital Pitié Salpêtrière

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

All participants

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline
CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72
Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline
Exploratory outcomes
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
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
Conversion to symptomatic non-AD cognitive disease
Atypical AD according to IWG 2014 criteria
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

Full Information

First Posted
March 14, 2023
Last Updated
April 7, 2023
Sponsor
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT05806697
Brief Title
Investigation of AlzHeimer's Predictors in Subjective Memory Complainers - Extension Study
Acronym
INSIGHT-2
Official Title
Investigation of AlzHeimer's Predictors in Subjective Memory Complainers - Extension Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 17, 2023 (Anticipated)
Primary Completion Date
June 2028 (Anticipated)
Study Completion Date
December 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Memory Complaint, Memory Disorders
Keywords
risks factors, brain amyloid load, neurosciences, neurology, memory complaint, memory disorders

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
All participants
Arm Type
Other
Intervention Type
Procedure
Intervention Name(s)
Electroencephalogram (EEG)
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Oculomotor tests
Intervention Description
All participants in the INSIGHT-2 study are invited to perform the oculomotor test, excepting subjects reporting oculomotor disorders.
Intervention Type
Procedure
Intervention Name(s)
MRI
Intervention Description
All INSIGHT-2 participants will undergo a baseline MRI (structural and resting state fMRI) a follow-up MRI at M12, M36 and M60.
Intervention Type
Radiation
Intervention Name(s)
18-F amyloid PET Scan
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
18F-fluorodeoxyglucose (FDG) PET Scan
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Blood sampling
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Lumbar puncture
Intervention Description
A lumbar puncture for cerebrospinal fluid (CSF) collection is proposed to all participants.
Primary Outcome Measure Information:
Title
The primary endpoint is the conversion to typical AD during the 5-year follow-up.
Description
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
Time Frame
every year through study completion, from baseline for 5 years (M60)
Secondary Outcome Measure Information:
Title
Change in Clinical Dementia Rating- Sum of Boxes (CDR-SB) score compared to baseline
Description
CDR-SB : Hughes, Br J Psychiatry 1982; 140: 566-72
Time Frame
Each 1 year from baseline for 5 years (M60)
Title
Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline
Description
Exploratory outcomes
Time Frame
Each 1 year from baseline for 5 years (M60)
Title
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)
Description
Exploratory outcomes
Time Frame
Each 1 year from baseline for 5 years (M60)
Title
Rate of change in biomarkers measured from blood, CSF, structural and functional neuroimaging (MRI), EEG and molecular neuroimaging (18F-FDG-PET and amyloid imaging)
Description
Exploratory outcomes
Time Frame
Each 1 year from baseline for 5 years (M60)
Title
Conversion to symptomatic non-AD cognitive disease
Description
Atypical AD according to IWG 2014 criteria
Time Frame
Each 1 year from baseline for 5 years (M60)
Title
Diagnosis of cerebral amyloid angiopathy based on V2.0 BOSTON criteria
Description
As described in the following reference: Charidimou et al., Lancet Neurol. 2022 Aug;21(8):714-725
Time Frame
Each 1 year from baseline for 5 years (M60)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadjia YOUNSI
Phone
+331 42 16 75 15
Email
nadjia.younsi@icm-institute.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stéphanie BOMBOIS, MD
Organizational Affiliation
Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Pitié Salpêtrière
City
Paris
State/Province
Ile De France
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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

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