Alzheimer Disease
Conditions
Keywords
Tau, Amyloid, MK-6240, Florbetaben, Racial/Ethnic Minority, Alzheimer's disease
Brief summary
The study employs tau positron emission tomography (PET) imaging in a well-characterized multi-racial/ethnic cohort to examine the extent to which tau pathology is associated with cognition, differences in tau pathology across racial/ethnic groups, and the relationship between MRI markers of small-vessel cerebrovascular disease and tau pathology. The study also investigates amyloid-dependent tau spreading.
Detailed description
Deposition of hyperphosphorylated tau protein is observed in several neurodegenerative diseases including Alzheimer's Disease (AD), progressive supranuclear palsy, corticobasal degeneration, chronic traumatic encephalopathy, and frontotemporal lobar degeneration. Tau is a microtubular protein and its native function is to provide structural support to neurons. Paired helical filaments composed of dysfunctional tau protein are found in several neurodegenerative diseases. In AD, the clinical progression of dementia has been shown to correlate with the amount and topographical spread of tau throughout the brain. Therefore, detecting and quantifying tau aggregate load in brain would have diagnostic and prognostic potential in clinical management of several neurological diseases. As disease modifying drugs that target tau are being developed, there is a critical need for a reliable method of detecting tau aggregates to confirm pathology in patients entering clinical trials.
Interventions
DRUG18F-MK-6240
Administration of 5 mCi of 18F-MK-6240 for tau PET.
DRUG18F-Florbetaben
Administration of 8.1 mCi as a slow single intravenous bolus (6 sec/mL) in a total volume of up to 10 mL of 18F-Florbetaben for Aβ PET imaging.
Sponsors
National Institute on Aging (NIA)
Adam Brickman
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 35 - 85 years * Have either mild cognitive impairment or mild clinical Alzheimer's disease; or have no problem with memory or thinking. * Able to participate in all scheduled evaluations and to complete all required tests and procedures * Considered likely to comply with the study protocol and to have a high probability of completing the study
Exclusion criteria
* Past or present history of a certain brain disease other than mild cognitive impairment or mild clinical Alzheimer's disease. * Certain significant medical conditions. Examples are uncontrolled epilepsy or multiple serious injuries. * Unable to lie still for PET scans. * Radiation exposure for research studies in the last year that would put you past allowable limits if included in this study. * Participation in the last year in a clinical trial for a disease modifying drug for AD unless it can be determined that your received placebo and not active drug. * Conditions that preclude entry into the scanner (e.g. claustrophobia, etc.). * Inability to have a catheter in your vein for the injection of the radioligand (dye). * Currently pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Regional SUVR Value for 18F-MK-6240 | 1 day | Regional standardized uptake value ratio (SUVR) for 18F-MK-6240 will be calculated to investigate associations with measures of memory, olfactory function, and cerebrovascular disease. |
| Number of Participants With Amyloid Positivity (Aβ+) for 18F-Florbetaben | 1 day | 18F-Florbetaben will be calculated to investigate the potential moderation of amyloid on the associations with tau. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Racially/ethnically diverse subjects with or without a positive family history of Alzheimer's disease (AD) will have one PET scan with 18F-MK-6240 over a 30 to 60-minute scanning period, and one PET scan with 18F-Florbetaben over a 20-minute scanning period. | 142 |
| Total | 142 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 36 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 71 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 142 participants |
| Sex: Female, Male Female | 89 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 142 |
| other Total, other adverse events | 19 / 142 |
| serious Total, serious adverse events | 0 / 142 |
Outcome results
Primary
Number of Participants With Amyloid Positivity (Aβ+) for 18F-Florbetaben
18F-Florbetaben will be calculated to investigate the potential moderation of amyloid on the associations with tau.
Time frame: 1 day
Population: 126 participants had complete PET scans with this tracer
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Amyloid Positivity (Aβ+) for 18F-Florbetaben | 12 Participants |
Primary
Regional SUVR Value for 18F-MK-6240
Regional standardized uptake value ratio (SUVR) for 18F-MK-6240 will be calculated to investigate associations with measures of memory, olfactory function, and cerebrovascular disease.
Time frame: 1 day
Population: 115 participants had complete PET scans with this tracer
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Regional SUVR Value for 18F-MK-6240 | 1.27 SUVR | Standard Deviation 0.23 |