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

Alzheimer Disease Clinical Trial

— INSIGHT-2  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05806697
• Other study ID #: C20-70
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 17, 2023
• Est. completion date: December 2029

Study information

• Verified date: April 2023
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Nadjia YOUNSI
• Phone: +331 42 16 75 15
• Email: nadjia.younsi[@]icm-institute.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: December 2029
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years to 95 Years

Eligibility

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).

Related Conditions & MeSH terms

• Alzheimer Disease
• Memory Complaint
• Memory Disorders

Intervention

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.
• Oculomotor tests
All participants in the INSIGHT-2 study are invited to perform the oculomotor test, excepting subjects reporting oculomotor disorders.
• 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 (ß+) emission and has a half-life of 109.77 min. This procedure will be done at baseline.
• 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.
• Lumbar puncture
A lumbar puncture for cerebrospinal fluid (CSF) collection is proposed to all participants.

Locations

Country	Name	City	State
France	Hôpital Pitié Salpêtrière	Paris	Ile De France

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Change in different neuroimaging, biological, electrophysiological and oculomotor parameters compared to baseline	Exploratory outcomes	Each 1 year from baseline for 5 years (M60)
Secondary	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)
Secondary	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)
Secondary	Conversion to symptomatic non-AD cognitive disease	Atypical AD according to IWG 2014 criteria	Each 1 year from baseline for 5 years (M60)
Secondary	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)