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MRI and PET Biomarkers for Cognitive Decline in Older Adults

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ClinicalTrials.gov Identifier: NCT03860857
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : March 11, 2019
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Michael Yassa, University of California, Irvine

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Cognitive Impairment Cognitive Decline Radiation: Amyloid PET scan Drug: Tau PET scan using MK-6240 Behavioral: Neurocognitive testing Other: MRI Phase 3

Detailed Description:
This study investigates the relationship between Alzheimer's disease (AD) pathology, brain structure and function, as well as cognition in non-demented older adults. The goal is to develop a more complete understanding of the factors that lead to cognitive decline in the elderly and progression to AD. The investigators will enroll 200 cognitively intact adults between the ages of 60-85 years old from the UCI Alzheimer's Disease Research Center or directly from the local community. Study procedures will include: 1) PET amyloid scans with Amyvid™ radiotracer (florbetapir-F18) and PET tau scans with [18F]MK6240 radiotracer; 2) High-resolution structural, functional, and diffusion MRI; and 3) Cognitive examinations. The investigators will track cognitive outcomes through longitudinal monitoring. Amyloid imaging will only be conducted once in the study at baseline, and MRI and tau PET imaging will be at baseline and Year 1. The investigators aim to identify the best combination of tests for predicting longitudinal cognitive/clinical decline. The proposed study will significantly inform the understanding of cognitive decline in the aging brain and allow investigators to better define preclinical AD and make recommendations for future intervention trials.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: MRI and PET Biomarkers for Cognitive Decline in Older Adults
Actual Study Start Date : May 1, 2018
Estimated Primary Completion Date : December 22, 2023
Estimated Study Completion Date : December 22, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Age 60-65 ApoE e4+
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 66-70 ApoE e4-
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 66-70 ApoE e4+
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 71-75 ApoE e4-
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 71-75 ApoE e4+
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 76-80 ApoE e4-
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 76-80 ApoE e4+
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 81-85 ApoE e4-
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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

Experimental: Age 81-85 ApoE e4+
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
Amyloid Positron Emission Tomography scan using radio tracer florbetapir-F18

Drug: Tau PET scan using MK-6240
Tau Positron Emission Tomography scan using radio tracer MK-6240
Other Name: tau PET

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

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




Primary Outcome Measures :
  1. Change in Clinical Dementia Rating - Sum of Box Score [ Time Frame: Years 4 and 5 of the grant ]
    A measure of cognitive/clinical decline


Secondary Outcome Measures :
  1. Change in lure discrimination index - objects [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the object pattern separation task

  2. Change in lure discrimination index - spatial [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the spatial pattern separation task

  3. Change in lure discrimination index - temporal [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of performance on the temporal pattern separation task

  4. Change in entorhinal cortical thickness [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of structural decline on MRI scans

  5. Change in perforant path integrity [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of structural connectivity decline on MRI scans

  6. Change in tau spatial distribution - advancing Braak stage [ Time Frame: Years 4 and 5 of the grant ]
    Key measure of tau spatial spread on tau PET scans



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Between the ages of 60 and 85;
  2. Speaks fluent English;
  3. Visual and auditory acuity adequate for neuropsychological and computerized testing;
  4. Good general health with no disease(s) expected to interfere with the study;
  5. Willing and able to participate for the duration of the study and in all study procedures including MRI and PET;
  6. Normal cognition defined as a Clinical Dementia Rating of 0 and a Mini-Mental State Examination score of 27 or higher.

Exclusion Criteria:

  1. Significant co-morbid neurologic disease such as Parkinson's disease, multiple sclerosis, brain cyst, tumor or aneurysm;
  2. Major health conditions such as uncontrolled diabetes mellitus, uncontrolled hypertension, nutritional deficiency or uncontrolled thyroid disease;
  3. Significant psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorder, major depressive disorder, or attention-deficit hyperactivity disorder;
  4. ADRC consensus diagnosis of dementia or mild cognitive impairment;
  5. Cognitive impairment when tested at baseline (defined as a score on any neuropsychological test of 1.5 SDs or more outside the age norm);
  6. Alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria);
  7. 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;
  8. PET contraindications, e.g. significant prior radiation exposure and pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03860857


Contacts
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Contact: Myra S Larson, BA 949-824-0314 mslarson@uci.edu
Contact: Blake A Miranda, BS 949-824-4094 bamirand@uci.edu

Locations
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United States, California
University of California, Irvine Recruiting
Irvine, California, United States, 92697
Contact: Myra S Larson, BA    949-824-0314    mslarson@uci.edu   
Contact: Blake A Miranda, BS    949-824-4094    bamirand@uci.edu   
Principal Investigator: Michael A Yassa, PhD         
Sponsors and Collaborators
University of California, Irvine
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Michael A Yassa, PhD University of California, Irvine
Study Director: Liv C McMillan, BS, CCRP University of California, Irvine

Additional Information:
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Responsible Party: Michael Yassa, Professor, University of California, Irvine
ClinicalTrials.gov Identifier: NCT03860857     History of Changes
Other Study ID Numbers: 2017-3832
R01AG053555-02 ( U.S. NIH Grant/Contract )
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Yassa, University of California, Irvine:
Alzheimer disease
cognitive impairment
mild cognitive impairment
biomarker
MRI
PET

Additional relevant MeSH terms:
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Dementia
Alzheimer Disease
Cognitive Dysfunction
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders