Alzheimer's Disease
Conditions
Brief summary
This study will test if two flortaucipir PET scans up to 4 weeks apart in healthy volunteers, MCI and AD subjects provide the same results.
Interventions
DRUGFlortaucipir F18
IV injection, 370 MBq (10 mCi), two doses up to four weeks apart
PROCEDUREBrain PET scan
positron emission tomography (PET) scan of the brain at 80-100 and 110-130 minutes after injection
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy Volunteers * Male or female subjects ≥ 50 years of age * Mini-mental state examination (MMSE) ≥ 29 * MCI Subjects * Male or female 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 * Probable AD Subjects * Male or female subjects ≥ 50 years of age * MMSE \> 10 * Meet clinical criteria for 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
Exclusion criteria
* Current clinically significant psychiatric disease * Evidence of structural brain abnormalities * Evidence of dementing illness other than AD * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test-Retest Reproducibility | 80-100 minutes postdose | Evaluate test-retest reproducibility of flortaucipir for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects |
Countries
United States
Participant flow
Recruitment details
Enrollment between Nov 2013 and May 2014
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteer Subjects Healthy males or females 50 years or older with no evidence of cognitive impairment
Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart
Brain PET scan: positron emission tomography (PET) scan of the brain | 6 |
| MCI Subjects Subjects 50 years or older with mild cognitive impairment (MCI)
Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart
Brain PET scan: positron emission tomography (PET) scan of the brain | 8 |
| Probable AD Subjects Subjects 50 years or older with probable Alzheimer's Disease (AD)
Flortaucipir F18: IV injection, 370 MBq (10 mCi), two doses up to four weeks apart
Brain PET scan: positron emission tomography (PET) scan of the brain | 10 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | Healthy Volunteer Subjects | MCI Subjects | Probable AD Subjects |
|---|---|---|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 8.4 | 62.8 years STANDARD_DEVIATION 9.5 | 70.3 years STANDARD_DEVIATION 5.4 | 74.4 years STANDARD_DEVIATION 7.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 6 Participants | 8 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Mini Mental Status Exam (MMSE) | 26.8 units on a scale STANDARD_DEVIATION 3.95 | 29.7 units on a scale STANDARD_DEVIATION 0.52 | 28.3 units on a scale STANDARD_DEVIATION 1.58 | 23.9 units on a scale STANDARD_DEVIATION 4.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 5 Participants | 8 Participants | 10 Participants |
| Region of Enrollment United States | 24 Participants | 6 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 16 Participants | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 10 |
| other Total, other adverse events | 1 / 6 | 0 / 8 | 3 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 10 |
Outcome results
Primary
Test-Retest Reproducibility
Evaluate test-retest reproducibility of flortaucipir for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects
Time frame: 80-100 minutes postdose
Population: All subjects with a valid test and re-test scan. The 80-100 minute scan was not done for one subject in the healthy volunteer group due to technical difficulties with the scanning apparatus
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Subjects | Test-Retest Reproducibility | Test Imaging | 1.342 standardized uptake value ratio (SUVr) | Standard Deviation 0.341 |
| All Subjects | Test-Retest Reproducibility | Retest Imaging | 1.355 standardized uptake value ratio (SUVr) | Standard Deviation 0.309 |
Comparison: Intraclass correlation coefficient \[ICC(2,1)\] analysis from Shrout and Fleiss95% CI: [0.935, 0.988]
Primary
Test-Retest Reproducibility
Evaluate test-retest reproducibility of 18F-AV-1451 for brain imaging of tau in healthy volunteers and subjects with cognitive impairment. Standard uptake value ratios (SUVRs) for each scan, normalized to the cerebellar crus. A combination volume of interest (VOI) = weighted average of parietal, temporal, and occipital regions was used. The protocol pre-specified that test-retest endpoint was to be calculated for the combined group of healthy volunteers and cognitively impaired subjects
Time frame: 110-130 minutes postdose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Subjects | Test-Retest Reproducibility | Test Imaging | 1.459 standardized uptake value ratio (SUVr) | Standard Deviation 0.455 |
| All Subjects | Test-Retest Reproducibility | Retest Imaging | 1.457 standardized uptake value ratio (SUVr) | Standard Deviation 0.396 |
Comparison: Intraclass correlation coefficient \[ICC(2,1)\] analysis from Shrout and Fleiss95% CI: [0.926, 0.986]