Biomarker Exploration in Aging, Cognition and Neurodegeneration

NCT03860857 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: 20173832R01AG053555
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to understand the factors that underlie changes in thinking and memory with increasing age. The investigators will test the usefulness of MRI, PET, and cognitive testing in detecting subtle changes in the brain that precede cognitive decline. An addendum to this study includes additional PET scans to examine the relationship between tau protein in the brain and cognitive decline. Tau is a protein that is known to form tangles in the areas of the brain important for memory, and these tau tangles are a hallmark of Alzheimer's disease. This sub-study research aims to look at the tau accumulation in the brain using an investigational drug called MK-6240, which is a radio tracer that gets injected prior to a positron emission tomography (PET) scan.

Conditions

Alzheimer Disease; Cognitive Impairment; Cognitive Decline

Keywords

Alzheimer disease; cognitive impairment; mild cognitive impairment; biomarker; MRI; PET

Outcome Measures

Primary Outcomes (1)

• Change in Clinical Dementia Rating - Sum of Box Score

  A measure of cognitive/clinical decline

  Years 4 and 5 of the grant

Secondary Outcomes (6)

• Change in lure discrimination index - objects

  Years 4 and 5 of the grant

• Change in lure discrimination index - spatial

  Years 4 and 5 of the grant

• Change in lure discrimination index - temporal

  Years 4 and 5 of the grant

• Change in entorhinal cortical thickness

  Years 4 and 5 of the grant

• Change in perforant path integrity

  Years 4 and 5 of the grant

Study Arms (9)

Age 60-65 ApoE e4+

EXPERIMENTAL

Participants in this cohort are between the ages of 60-65 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 66-70 ApoE e4-

EXPERIMENTAL

Participants in this cohort are between the ages of 66-70 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 66-70 ApoE e4+

EXPERIMENTAL

Participants in this cohort are between the ages of 66-70 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 71-75 ApoE e4-

EXPERIMENTAL

Participants in this cohort are between the ages of 71-75 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 71-75 ApoE e4+

EXPERIMENTAL

Participants in this cohort are between the ages of 71-75 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 76-80 ApoE e4-

EXPERIMENTAL

Participants in this cohort are between the ages of 76-80 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 76-80 ApoE e4+

EXPERIMENTAL

Participants in this cohort are between the ages of 76-80 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 81+ ApoE e4-

EXPERIMENTAL

Participants in this cohort are between the ages of 81-85 and are not ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Age 81+ ApoE e4+

EXPERIMENTAL

Participants in this cohort are between the ages of 81-85 and are ApoE e4 carriers. All participants in this cohort will complete the Amyloid PET scan, Tau PET scan using MK-6240, MRI scans, and neurocognitive testing.

Radiation: Amyloid PET scan; Drug: Tau PET scan using MK-6240; Behavioral: Neurocognitive testing; Other: MRI

Interventions

Amyloid PET scan RADIATION

Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Age 60-65 ApoE e4+; Age 66-70 ApoE e4+; Age 66-70 ApoE e4-; Age 71-75 ApoE e4+; Age 71-75 ApoE e4-; Age 76-80 ApoE e4+; Age 76-80 ApoE e4-; Age 81+ ApoE e4+; Age 81+ ApoE e4-

Tau PET scan using MK-6240 DRUG

Tau Positron Emission Tomography scan using radio tracer MK-6240

Also known as: tau PET

Age 60-65 ApoE e4+; Age 66-70 ApoE e4+; Age 66-70 ApoE e4-; Age 71-75 ApoE e4+; Age 71-75 ApoE e4-; Age 76-80 ApoE e4+; Age 76-80 ApoE e4-; Age 81+ ApoE e4+; Age 81+ ApoE e4-

Neurocognitive testing BEHAVIORAL

A battery of clinical neuropsychological assessments and computerized cognitive tasks will be used to test participants' memory and cognitive abilities.

Age 60-65 ApoE e4+; Age 66-70 ApoE e4+; Age 66-70 ApoE e4-; Age 71-75 ApoE e4+; Age 71-75 ApoE e4-; Age 76-80 ApoE e4+; Age 76-80 ApoE e4-; Age 81+ ApoE e4+; Age 81+ ApoE e4-

MRI OTHER

High-resolution structural, functional, and diffusion Magnetic Resonance Imaging scans will be collected during the study.

Age 60-65 ApoE e4+; Age 66-70 ApoE e4+; Age 66-70 ApoE e4-; Age 71-75 ApoE e4+; Age 71-75 ApoE e4-; Age 76-80 ApoE e4+; Age 76-80 ApoE e4-; Age 81+ ApoE e4+; Age 81+ ApoE e4-

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 60 or older;
• Speaks fluent English or Spanish;
• Visual and auditory acuity adequate for neuropsychological and computerized testing;
• Good general health with no disease(s) expected to interfere with the study;
• Willing and able to participate for the duration of the study and in all study procedures including MRI and PET;
• Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 25 or higher. FAST Stage 1 or 2.
• Subjective memory or other cognitive complaints will be included.

You may not qualify if:

• Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
• Existing diagnosis of dementia or mild cognitive impairment;
• Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
• MRI contraindications, e.g. pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body. Females who are pregnant or trying to get pregnant are also excluded;
• PET contraindications, e.g. significant prior radiation exposure and pregnancy.

Sponsors & Collaborators

• University of California, Irvine: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of California, Irvine

Irvine, California, 92697, United States

RECRUITING

Related Publications (5)

• Stevenson RF, Reagh ZM, Chun AP, Murray EA, Yassa MA. Pattern Separation and Source Memory Engage Distinct Hippocampal and Neocortical Regions during Retrieval. J Neurosci. 2020 Jan 22;40(4):843-851. doi: 10.1523/JNEUROSCI.0564-19.2019. Epub 2019 Nov 20.

  PMID: 31748377 RESULT

• Holbrook AJ, Tustison NJ, Marquez F, Roberts J, Yassa MA, Gillen DL; Alzheimer's Disease Neuroimaging Initiative section sign. Anterolateral entorhinal cortex thickness as a new biomarker for early detection of Alzheimer's disease. Alzheimers Dement (Amst). 2020 Aug 25;12(1):e12068. doi: 10.1002/dad2.12068. eCollection 2020.

  PMID: 32875052 RESULT

• Chappel-Farley MG, Mander BA, Neikrug AB, Stehli A, Nan B, Grill JD, Yassa MA, Benca RM. Symptoms of obstructive sleep apnea are associated with less frequent exercise and worse subjective cognitive function across adulthood. Sleep. 2022 Mar 14;45(3):zsab240. doi: 10.1093/sleep/zsab240.

  PMID: 34604910 RESULT

• Adams JN, Kim S, Rizvi B, Sathishkumar M, Taylor L, Harris AL, Mikhail A, Keator DB, McMillan L, Yassa MA. Entorhinal-Hippocampal Circuit Integrity Is Related to Mnemonic Discrimination and Amyloid-beta Pathology in Older Adults. J Neurosci. 2022 Nov 16;42(46):8742-8753. doi: 10.1523/JNEUROSCI.1165-22.2022. Epub 2022 Oct 27.

  PMID: 36302636 RESULT

• Adams JN, Marquez F, Larson MS, Janecek JT, Miranda BA, Noche JA, Taylor L, Hollearn MK, McMillan L, Keator DB, Head E, Rissman RA, Yassa MA. Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults. Alzheimers Dement (Amst). 2023 Apr 5;15(2):e12419. doi: 10.1002/dad2.12419. eCollection 2023 Apr-Jun.

  PMID: 37035460 RESULT

Related Links

• BEACoN (Biomarker Exploration in Aging, Cognition, and Neurodegeneration) study website

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Michael A Yassa, PhD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

• Liv C McMillan, BS, CCRP

  University of California, Irvine

  STUDY DIRECTOR

Central Study Contacts

Evelyn Chang, BA

CONTACT

949-824-0904; beacon@uci.edu

Novelle Meza, BS

CONTACT

949-824-5049; njmeza@uci.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: All participants will complete the same study procedures, including the tau PET scans with investigational radio tracer 18F-MK6240. The arms define the age range and APOE status of the participants, with each having their own enrollment target.

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: March 4, 2019
• Study Start: May 1, 2018
• Primary Completion (Estimated): December 22, 2026
• Study Completion (Estimated): December 22, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)