BioFINDER-Brown: Examination of Alzheimer's Disease Biomarkers

• Conditions: Dementia; Mild Cognitive Impairment; Alzheimer Disease
• Interventions: Diagnostic Test: Flutemetamol F18 Injection; Diagnostic Test: [18F]-RO6958948 Injection; Diagnostic Test: [18F]-MK-6240 Injection

• Registration Number: NCT05457998
• Lead Sponsor: Butler Hospital

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 subject participation lasting approximately 4 years. Disclosure of AD risk assessments will be an optional procedure. Two PET imaging sub-studies will also be optional.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-11
• Study First Submitted QC: 2022-07-11
• Study First Posted: 2022-07-14
• Study Start: 2023-06-14
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-17
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Individuals between the ages of 50 and 80 years old (inclusive)
• Score of 16 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
• Participants in the 50-60 age range will additionally need to meet at least one of the following: (1) First degree family history of dementia with onset before age 75; (2) APOE e4 allele carrier; or (3) Prior elevated result on amyloid PET or amyloid CSF testing
• 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
• History of significant brain injury or other known neurologic disease or insult, resulting in lasting cognitive sequelae that would confound the assessment and staging of potential neurodegenerative disease (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, encephalitis or other brain infection, epilepsy or stroke with lasting impairment to cognitive function).
• Current serious or unstable systemic illness or organ failure that, in the PI's judgement, would make it difficult to participate in the study (e.g., such as terminal cancer, cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions ). History of cancer is acceptable with at least one year in remission with a good prognosis.
• Individuals with clinically significant depression, bipolar disorder, anxiety, or suicidal ideations within the past year 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 year 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Main study population: Cognitively unimpaired individuals (50-80 y)	Flutemetamol F18 Injection	Participants will be enrolled based on a predetermined ratio of Alzheimer's Disease plasma and PET biomarker risk levels (e.g., as P-tau217 and amyloid PET). FOLLOW-UP FOR 4 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 screening/baseline and 24 months. An additional amyloid PET scan will be performed at 48 months.
Sub-group 1: Optional Tau PET imaging sub-study	[18F]-RO6958948 Injection	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.
Sub-group 2: Optional Tau PET tracer comparison sub-study	[18F]-MK-6240 Injection	An optional tau PET tracer comparison sub-study will be conducted in 30 subjects from the main study population who elect to participate. Tau PET scans with 2 tracers (\[18F\]RO-948 and \[18F\]MK-6240) will be performed at baseline and 24 months. An additional Tau PET scan with \[18F\]RO-948 will be performed at 48 months.
Sub-group 2: Optional Tau PET tracer comparison sub-study	[18F]-RO6958948 Injection	An optional tau PET tracer comparison sub-study will be conducted in 30 subjects from the main study population who elect to participate. Tau PET scans with 2 tracers (\[18F\]RO-948 and \[18F\]MK-6240) will be performed at baseline and 24 months. An additional Tau PET scan with \[18F\]RO-948 will be performed at 48 months.

Primary Outcome Measures

Name	Time	Method
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 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 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

Name	Time	Method
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 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 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.

Trial Locations

Locations (1)

Butler Hospital Memory and Aging Program; 🇺🇸 Providence, Rhode Island, United States