A Phase 2/3 cross-sectional and longitudinal observational study evaluating imaging characteristics of flortaucipir in control subjects and patients with clinically defined MCI and AD dementia (AD).
This study was conducted in 2 phases: a Phase 2 Exploratory Phase and a Phase 3 Confirmatory Phase. An overarching goal of the Exploratory Phase of this protocol was to further investigate the pattern of flortaucipir PET imaging across the disease course, in cognitively healthy subjects through patients with cognitive decline. To accomplish this goal, the protocol investigated flortaucipir results in younger and older cognitively healthy normal volunteers and patients with clinical diagnoses for cognitive complaints, ranging from MCI to mild and moderate AD dementia. Additionally, the Exploratory Phase of this protocol investigated relationships between flortaucipir PET signal and cognitive decline over the 18-month study period. The second, Confirmatory Phase of the study was designed to provide independent validation of the relationships observed in the exploratory analyses of the first phase. In particular, the goal of the second phase was to confirm the relationship between flortaucipir uptake in the brain as measured by PET signals at baseline and the subsequent rate of cognitive decline observed over the 18-month longitudinal follow up.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
SINGLE
Enrollment
383
positron emission tomography (PET) scan of the brain
Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline
Confirm the relationship between neocortical flortaucipir uptake and the subsequent rate of cognitive decline at longitudinal follow up that was observed in the Exploratory Phase of the study. Patients were assigned to groups by majority classification of the flortaucipir positron emission tomography (PET) scan by five independent imaging physicians. Clinically meaningful cognitive and functional deterioration was defined as a 1 point or greater worsening on clinical dementia rating - sum of boxes (CDR-SB) score over the follow-up period.
Time frame: between baseline and 18 months
Exploratory Phase: Cross-sectional Flortaucipir Imaging Results
Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline scan
Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status
Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.
Time frame: baseline and 18 months
Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read
This analysis used dichotomized CDR-SB change as a truth standard (1 point or more worsening = true positive vs. less than 1 point worsening = true negative) to assess the diagnostic performance of baseline Advanced AD tau status (τAD++) as determined by flortaucipir scan interpretation. Sensitivity and Specificity were calculated for each of the 5 independent imaging readers. Sensitivity is the percentage of true positive cases correctly identified by an Advanced AD pattern scan. Specificity is the percentage of true negative cases correctly identified by scans that were not classified as Advanced AD pattern.
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Banner Alzheimer's Institute
Phoenix, Arizona, United States
Four Peaks Neurology
Scottsdale, Arizona, United States
Mayo Clinic
Scottsdale, Arizona, United States
Banner Sun Health Research Institute
Sun City, Arizona, United States
UC Irvine
Irvine, California, United States
Hoag Memorial
Newport Beach, California, United States
Norther California PET Imaging Center
Sacramento, California, United States
UC Davis
Sacramento, California, United States
UC San Francisco
San Francisco, California, United States
Neurological Research Institute
Santa Monica, California, United States
...and 17 more locations
Time frame: baseline and 18 months
Exploratory Phase: Correlation Between Flortaucipir SUVr and Age
Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Time frame: baseline scan