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OpenTrials
Enrolling by invitation

NCT Number: NCT06416072

Alzheimer's Plasma Extension

The goal of this observational study is to learn how Alzheimer's disease-related blood biomarkers, brain amyloid, and memory and thinking abilities change over time. The study will include up to 3,000 people who previously did not qualify for an anti-amyloid Alzheimer's disease prevention trial based on their amyloid eligibility. Participants may have previously screened for the AHEAD 3-45 Study, A4 Study, or another anti-amyloid Alzheimer's disease prevention trial.

The main questions this study aims to answer are:

* Can Alzheimer's disease-related blood tests help predict future buildup of amyloid in the brain? * How are changes in Alzheimer's disease-related blood biomarkers related to changes in brain amyloid, memory, thinking, and self-reported cognitive function? * Do these changes differ based on factors such as sex, APOE genetic status, race, ethnicity, socioeconomic status, or social factors?

Participants will be followed for about 6 years. They will complete memory and thinking assessments and questionnaires and provide blood samples. Some participants may also be asked to take part in optional activities, including brain imaging with positron emission tomography (PET) or magnetic resonance imaging (MRI), digital cognitive assessments, and questionnaires about habits and social factors.

Enrolling by invitation

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Key information

Conditions

Preclinical Alzheimer's Disease Alzheimer Disease Alzheimer's Disease (AD) Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Plaque, Amyloid Tauopathies

Age range

55 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Alabama, Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Documentation of the participant's informed consent to study procedures and for the use of protected health information (HIPAA Authorization, or local, regional or country-specific equivalent). Informed consent processes and documentation must adhere to state laws/local requirements, including consent provided by the participant's legally authorized representative (LAR), responsible next of kin, surrogate consent with assent, etc.
  • Previously consented to participate in an anti-amyloid preclinical AD study (e.g., AHEAD 3-45, A4 or other anti-amyloid preclinical AD study).
  • Has screening results that did not meet amyloid eligibility criteria for an anti-amyloid preclinical AD trial (e.g., AHEAD 3-45, A4, or other anti-amyloid preclinical AD study).
  • As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all required procedures for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures.

For participants who screen failed from the AHEAD 3-45 Study:

  • Has AHEAD 3-45 screening plasma biomarker results required for determining eligibility to participate in the AHEAD 3-45 Study.

Exclusion criteria

  • Current treatment with an FDA approved medication for Alzheimer's disease, including prior or current treatment with a prohibited medication.
  • Enrollment in another investigational study, or intake of investigational drug, within 30 days prior to screening, or five half-lives of the investigational drug, whichever is longer, unless it can be documented that the participant was in the placebo treatment arm.
  • Screen failed from an anti-amyloid preclinical AD trial (e.g. AHEAD 3-45, A4 or other anti-amyloid preclinical AD trial) due to not meeting basic inclusion criteria (i.e., age requirement; current diagnosis of AD dementia).

For participants participating in the optional amyloid PET imaging sub-study:

  • Is pregnant or breastfeeding.

Treatment and study plan

NAV4694

Radiation

Amyloid PET imaging with NAV4694 injection

Other names: [18F]NAV4694

Primary outcomes

  1. Rate of change from Baseline through Month 72 in plasma beta-amyloid (Aβ) 40 or 42 ratio

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

    Change in plasma Aβ42/Aβ40 ratio over the longitudinal follow-up period will be assessed using repeated blood-based biomarker measurements.

  2. Rate of change from Baseline through Month 72 in plasma phosphorylated tau (ptau) 217

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

    Assess longitudinal changes from initial visit in plasma phosphorylated tau (ptau) 217 ratio using a proteomics assay

Secondary outcomes

  1. Rate of Change from Baseline through Month 72 as measured by the Preclinical Alzheimer Cognitive Composite 5 (PACC5)

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

    The Preclinical Alzheimer Cognitive Composite 5 (PACC5) is a composite measure of episodic memory, timed executive function, semantic memory, and global cognition. It includes: Free and Cued Selective Reminding Test (FCSRT), using the Free + Total Free and Cued Recall score (0-96, higher scores indicate better performance); delayed Paragraph Recall (0-25, higher scores indicate better recall); Digit Symbol Substitution Test (DSST), number correctly completed in 90 seconds (0-91, higher scores indicate better performance); Mini-Mental State Examination (MMSE) (0-30, higher scores indicate better performance); and Category Fluency, number of appropriate words generated, with higher scores indicating better performance.

  2. Rate of Change from Baseline through Month 72 as measured Cognitive Function Index (CFI)

    Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60, and Month 72

    The participant-reported Cognitive Function Index (CFI) assesses the participant's perceived ability to perform high-level functional tasks in daily life and overall cognitive functional ability. Only the participant-CFI portion will be administered. Participants rate their own abilities using 18 questions. The total participant-CFI score ranges from 0 (minimum) to 18 (maximum), with higher scores indicating greater impairment. The CFI may be self-administered or completed as an interview conducted by clinical site personnel in person or, if necessary, over the phone.

Other outcomes

  1. Change in Amyloid Positron Emission Tomography (PET)

    Time frame: Initial amyloid PET to longitudinal amyloid PET, approximately 4 years (plus or minus 1 year)

    Change in brain amyloid levels as measured by amyloid positron emission tomography (PET) imaging. Longitudinal amyloid PET will be compared with the participant's initial amyloid PET scan to assess change in brain amyloid over time.

Sponsors and collaborators

Lead sponsor

University of Southern California

Other

Collaborators

  • Alzheimer's Association
  • Alzheimer's Clinical Trials Consortium (ACTC)
  • Alzheimer's Therapeutic Research Institute
  • National Institute on Aging (NIA)

Registry information

Acronym: APEX

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
May 16, 2024
Registry last updated
Aug 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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