BioFINDER-Brown: Examination of Alzheimer's Disease Biomarkers

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.

Study Overview

• Status: Recruiting
• Conditions: Dementia; Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Diagnostic test: Flutemetamol F18 Injection; Diagnostic test: [18F]-RO6958948 Injection; Diagnostic test: [18F]-MK-6240 Injection

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Tara Tang, BA; Phone Number: 401-455-6402; Email: memory@butler.org
• Study Contact Backup: Name: Philip Caffery, PhD; Phone Number: 21004 401-455-6200; Email: pcaffery@butler.org

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • Butler Hospital Memory and Aging Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted in up to 200 subjects between the ages of 50-80 who are cognitively unimpaired. Participants must also pass all inclusion/exclusion criteria.

Description

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
• 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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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
Main study population: Cognitively unimpaired individuals (50-80 y); 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.	Diagnostic test: Flutemetamol F18 Injection; PET imaging of Abeta amyloid; Other Names: Vizamyl
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. 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.	Diagnostic test: [18F]-RO6958948 Injection; PET imaging of Tau aggregates; Diagnostic test: [18F]-MK-6240 Injection; PET imaging of Tau aggregates

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: Butler Hospital
• Collaborators: Eli Lilly and Company; GE Healthcare; Hoffmann-La Roche; Brown University; University of Rhode Island; The Warren Alpert Foundation
• Investigators: Principal Investigator: Stephen Salloway, MD,MS, Butler Hospital Memory and Aging Program

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 11, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Biomarker; tau; PET; Early diagnosis; β-amyloid; Cognitive test
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Flutemetamol
• Other Study ID Numbers: 1745146

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No