BioFINDER-Brown: Examination of Alzheimer's Disease Biomarkers

Sponsor

Butler Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05457998

Collaborator

The Warren Alpert Foundation (Other), Brown University (Other), University of Rhode Island (Other), Hoffmann-La Roche (Industry), Eli Lilly and Company (Industry), GE Healthcare (Industry)

200

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This research study aims to examine biomarkers of Alzheimer's disease as early as possible which could potentially be a screening tool for the general population. This observational study will take place at the Memory and Aging Program at Butler Hospital. The study will enroll up to 200 cognitively healthy subjects aged 50 to 80 years with ongoing recruitment and enrollment for 2 years and participant participation lasting approximately 5 years. Disclosure of AD risk assessments will be an optional procedure. Two PET imaging sub-studies will also be optional.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Mild Cognitive Impairment Dementia	Diagnostic Test: Flutemetamol F18 Injection Diagnostic Test: [18F]-RO6958948 Injection Diagnostic Test: [18F]-MK-6240 Injection Diagnostic Test: [18F]-GTP-1 Injection

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

BioFINDER-Brown: Examination of Alzheimer's Disease Biomarkers

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2027

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Main study population: Cognitively unimpaired individuals (50-80 y) This study will be conducted in up to 200 subjects between the ages of 50-80 who are cognitively unimpaired with ongoing recruitment and enrollment for 2 years and participant follow-up for 5 years. Following analysis of blood plasma at screening, all p-tau 217 plasma positive participants will be enrolled and scheduled for the baseline visit. A randomly selected 1/10 of all p-tau 217 plasma negative participants will also be enrolled. We will enroll participants until we have reached a sample size where 2/3 of participants are amyloid positive. FOLLOW-UP FOR 5 YEARS: Cognitive testing, blood draws and retinal imaging will be conducted at baseline and 12 months. Cognitive testing and blood draws will be conducted at 24 months and 36 months. MRI and Amyloid PET scans will be performed at baseline and 24 months. An additional amyloid PET scan will be performed at 48 months.	Diagnostic Test: Flutemetamol F18 Injection PET imaging of Abeta amyloid Other Names: Vizamyl
Sub-group 1: Optional Tau PET imaging sub-study An optional tau PET imaging sub-study will be conducted in 70 subjects from the main study population who elect to participate. If enrolled in the optional tau PET imaging sub-study, participants will have three tau PET scans with [18F]RO-948: at baseline, 24 months, and 48 months.	Diagnostic Test: [18F]-RO6958948 Injection PET imaging of Tau aggregates
Sub-group 2: Optional Tau PET tracer comparison sub-study An optional tau PET tracer comparison sub-study will be conducted in 30 subjects from the main study population who elect to participate. These individuals will be amyloid positive as determined by Flutemetamol amyloid PET scan. Tau PET scans with 3 tracers ([18F]RO-948, [18F]MK-6240, and [18F]GTP-1) will be performed at baseline and 24 months. An additional Tau PET scan with [18F]RO-948 will be performed at 48 months.	Diagnostic Test: [18F]-RO6958948 Injection PET imaging of Tau aggregates Diagnostic Test: [18F]-MK-6240 Injection PET imaging of Tau aggregates Diagnostic Test: [18F]-GTP-1 Injection PET imaging of Tau aggregates

Arm

Intervention/Treatment

Main study population: Cognitively unimpaired individuals (50-80 y)

This study will be conducted in up to 200 subjects between the ages of 50-80 who are cognitively unimpaired with ongoing recruitment and enrollment for 2 years and participant follow-up for 5 years. Following analysis of blood plasma at screening, all p-tau 217 plasma positive participants will be enrolled and scheduled for the baseline visit. A randomly selected 1/10 of all p-tau 217 plasma negative participants will also be enrolled. We will enroll participants until we have reached a sample size where 2/3 of participants are amyloid positive. FOLLOW-UP FOR 5 YEARS: Cognitive testing, blood draws and retinal imaging will be conducted at baseline and 12 months. Cognitive testing and blood draws will be conducted at 24 months and 36 months. MRI and Amyloid PET scans will be performed at baseline and 24 months. An additional amyloid PET scan will be performed at 48 months.

Diagnostic Test: Flutemetamol F18 Injection

PET imaging of Abeta amyloid

Other Names:

Vizamyl

Sub-group 1: Optional Tau PET imaging sub-study

An optional tau PET imaging sub-study will be conducted in 70 subjects from the main study population who elect to participate. If enrolled in the optional tau PET imaging sub-study, participants will have three tau PET scans with [18F]RO-948: at baseline, 24 months, and 48 months.

Diagnostic Test: [18F]-RO6958948 Injection

PET imaging of Tau aggregates

Sub-group 2: Optional Tau PET tracer comparison sub-study

An optional tau PET tracer comparison sub-study will be conducted in 30 subjects from the main study population who elect to participate. These individuals will be amyloid positive as determined by Flutemetamol amyloid PET scan. Tau PET scans with 3 tracers ([18F]RO-948, [18F]MK-6240, and [18F]GTP-1) will be performed at baseline and 24 months. An additional Tau PET scan with [18F]RO-948 will be performed at 48 months.

Diagnostic Test: [18F]-RO6958948 Injection

PET imaging of Tau aggregates

Diagnostic Test: [18F]-MK-6240 Injection

PET imaging of Tau aggregates

Diagnostic Test: [18F]-GTP-1 Injection

PET imaging of Tau aggregates

Outcome Measures

Primary Outcome Measures

Rate of change in plasma biomarkers [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]
Validate and assess longitudinal changes from baseline in plasma amyloid, phosphorylated tau (p-tau) and other fluid biomarkers (e.g., neurofilament light).
Rate of change in cerebral amyloid pathology [Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 5 years after baseline.]
Longitudinal assessment of cerebral amyloidosis based on amyloid PET imaging.
Rate of change in Tau PET measures [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]
Longitudinal assessment of cerebral tau accumulation based on tau PET imaging.

Secondary Outcome Measures

Rate of cognitive decline as measured by traditional cognitive and behavioral assessments [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]
Rate of cognitive decline as measured by digital cognitive assessments [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]
Rate of change in retinal imaging metrics [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]
Rate of change in psychological wellness as measured by the Geriatric Depression Scale [Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Individuals between the ages of 50 and 80 years old (inclusive)
Score of 12 or above on the MoCA telephone
Score of 27 or greater on the MMSE for individuals aged 50 to 64 years old or a score of 26 or greater for individuals aged 65 to 80 years old
Conversationally fluent in English to the extent that an interpreter is not necessary for comprehension of the study information, procedures, and cognitive tests.
If participants elect to participate in the optional disclosure procedure, they will be required to have an appropriate study partner who agrees to participate in the study and who is intellectually, visually, and auditory capable, and conversationally fluent in English to the extent that an interpreter is not necessary.
Adequate visual and auditory acuity to allow neuropsychological testing.
Participants must be willing and able to provide written informed consent.

Exclusion Criteria:

Diagnosis of mild cognitive impairment or dementia
Current neurological condition that might impact cognition or performance on cognitive assessments, e.g., Huntington's disease, Parkinson's disease, Parkinsonism due to multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Shy Drager Syndrome (SDS) or other neuro-degenerative dementias
History of severe brain injury or head trauma resulting in a protracted loss of consciousness.
History of stroke(s) with a lasting impairment to cognitive function.
History within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis).
Current diagnosis of epilepsy - childhood epilepsy or febrile seizures are not exclusionary.
A history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post treatment. History of in situ cancers that have been and are being treated and monitored are not exclusionary.
Current serious or unstable medical condition or illness including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that could interfere with the assessments of the study.
Individuals with clinically significant depression, bipolar disorder, anxiety, or suicidal ideations within the last 5 years as defined by the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
A history of schizophrenia as defined by the most current version of the DSM.
History within the past 5 years of chronic alcohol or drug abuse/dependence as defined by the most current version of the DSM.
Marijuana use is acceptable, but frequent users will be asked to abstain from use within 24 hours of any assessments.
Refusing or unable to complete any study procedures.
Currently enrolled in another study which involves clinical drug trial or other medical intervention.