Analysis of 18F-AV-1451 PET Imaging in Cognitively Healthy, MCI, and AD Subjects
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT02016560
- Lead Sponsor
- Avid Radiopharmaceuticals
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 383
Exploratory Cognitively Healthy Subjects
- ≥ 20 to ≤ 40 years of age OR ≥ 50 years of age
- Mini-mental state examination (MMSE) ≥ 29
- No significant history of cognitive impairment
Exploratory MCI Subjects
- ≥ 50 years of age
- MMSE ≥ 24
- Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD
- Have a study partner that can report on subject's activities of daily living
Exploratory AD Subjects
- ≥ 50 years of age
- MMSE > 10
- Have possible or probable AD based on the NIA-AA working group's diagnostic guidelines for AD
- Have a study partner that can report on subject's activities of daily living
Confirmatory Subjects
- ≥ 50 years of age
- MMSE ≥ 20 and ≤ 27
- Cognitively impaired subjects with either MCI or dementia with a suspected neurodegenerative cause
- Have a study partner that can report on subject's activities of daily living
- Current clinically significant psychiatric disease
- Evidence of structural brain abnormalities
- History of moderate or severe traumatic brain injury
- Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes
- Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
- History of alcohol or substance abuse or dependence
- Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
- Have received or participated in a trial with investigational medications in the past 30 days
- Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Exploratory MCI Subjects Flortaucipir F18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Exploratory Cognitively Healthy Subjects Brain PET Scan Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie \[mCi\]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline. Confirmatory Subjects Flortaucipir F18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline. Confirmatory Subjects Brain PET Scan Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline. Exploratory Cognitively Healthy Subjects florbetapir F 18 Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie \[mCi\]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline. Exploratory AD Subjects Flortaucipir F18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Exploratory AD Subjects Brain PET Scan Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Exploratory MCI Subjects Brain PET Scan Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Confirmatory Subjects florbetapir F 18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline. Exploratory MCI Subjects florbetapir F 18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Exploratory AD Subjects florbetapir F 18 Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months. Exploratory Cognitively Healthy Subjects Flortaucipir F18 Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie \[mCi\]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
- Primary Outcome Measures
Name Time Method Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline between baseline and 18 months 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.
Exploratory Phase: Cross-sectional Flortaucipir Imaging Results baseline scan 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.
Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status baseline and 18 months Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.
- Secondary Outcome Measures
Name Time Method Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read baseline and 18 months 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.
Exploratory Phase: Correlation Between Flortaucipir SUVr and Age baseline scan 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.
Trial Locations
- Locations (27)
UC Irvine
🇺🇸Irvine, California, United States
Neurological Research Institute
🇺🇸Santa Monica, California, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Four Peaks Neurology
🇺🇸Scottsdale, Arizona, United States
Quantum Laboratories
🇺🇸Deerfield Beach, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hoag Memorial
🇺🇸Newport Beach, California, United States
Center for Clinical Imaging Research
🇺🇸Saint Louis, Missouri, United States
Meridien Research
🇺🇸Saint Petersburg, Florida, United States
Boston University
🇺🇸Boston, Massachusetts, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
UC San Francisco
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Independent Imaging
🇺🇸West Palm Beach, Florida, United States
21st Century Oncology
🇺🇸Fort Myers, Florida, United States
Alzheimer's Disease Center
🇺🇸Quincy, Massachusetts, United States
Center for Brain Health - NYU Langone Medical Center
🇺🇸New York, New York, United States
Las Vegas Radiology
🇺🇸Las Vegas, Nevada, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Norther California PET Imaging Center
🇺🇸Sacramento, California, United States
UC Davis
🇺🇸Sacramento, California, United States
Molecular NeuroImaging
🇺🇸New Haven, Connecticut, United States
Sandlake Imaging
🇺🇸Orlando, Florida, United States
USF Health Byrd Alzheimer's Center
🇺🇸Tampa, Florida, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States