- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00857415
Phase III Study of the Correlation Between Florbetapir F18 PET Imaging and Amyloid Pathology in the Brain
A Phase III Study of the Correlation Between Florbetapir F 18 (18F-AV-45) PET Imaging and Amyloid Pathology
Study Overview
Detailed Description
There will be two primary analyses:
- The first primary analysis will evaluate the correlation between the blinded readers' rating of amyloid plaque density on the PET scan and the cortical amyloid plaque density at autopsy.
- The second primary analysis will evaluate the specificity of the blinded readers' rating of presence or absence of amyloid plaque density on the PET scan
For the autopsy population, subjects will be enrolled from various end-of-life (e.g. hospice / hospital / nursing home) and late-life (longitudinal studies of aging) populations. Enrollment will include subjects with various levels of cognitive status, ranging from cognitively normal through dementia. It is expected that amyloid plaque density in this elderly population will range from very low (normal aging) through moderate (e.g. cognitively normal subjects with asymptomatic amyloid deposits or mild cognitive impairment (MCI) subjects with intermediate levels of amyloid deposits) to very high (subjects with AD). The study will also enroll younger healthy subjects presumably devoid of amyloid in the specificity cohort.
Screening assessments may take place over several days and will include collection of demographic information, diagnostic interview, and safety assessments. At the time of screening, subjects or caregivers will be asked to provide consent for brain donation if they are not already enrolled in a brain donation program affiliated with this study, in addition to providing informed consent for the screening and imaging procedures in the study.
Subjects who qualify for the study will have a catheter placed for intravenous (i.v.) administration of florbetapir F 18. Subjects will receive a single i.v. bolus of 370 MBq (10 mCi) of florbetapir F 18 followed by brain PET imaging for 10 minutes duration, beginning approximately 50 minutes post-injection. Vital signs and safety labs will be obtained prior to the administration of florbetapir F 18 and at the completion of the imaging session. Adverse events will be continuously monitored during the imaging session. Subjects who experience an adverse event will not be discharged until the event has been resolved or stabilized.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Arizona
-
Phoenix, Arizona, United States, 85006
- Research site
-
Scottsdale, Arizona, United States, 85258
- Research site
-
Sun City, Arizona, United States, 85351
- Research site
-
-
Arkansas
-
Little Rock, Arkansas, United States, 72211
- Research site
-
-
California
-
Irvine, California, United States, 92697
- Research site
-
San Francisco, California, United States, 94109
- Research site
-
-
Florida
-
Fort Myers, Florida, United States, 33912
- Research site
-
Miami, Florida, United States, 33137
- Research site
-
Miami Beach, Florida, United States, 33140
- Research site
-
Miami Springs, Florida, United States, 33166
- Research site
-
Orlando, Florida, United States, 32835
- Research site
-
Sarasota, Florida, United States, 34231
- Research site
-
St. Petersburg, Florida, United States, 33709
- Research site
-
West Palm Beach, Florida, United States, 33407
- Research site
-
-
Maryland
-
Baltimore, Maryland, United States, 21221
- Research site
-
-
Mississippi
-
Hattiesburg, Mississippi, United States, 39401
- Research site
-
-
Missouri
-
St. Louis, Missouri, United States, 63141
- Research site
-
-
New York
-
Albany, New York, United States, 12208
- Research site
-
New Hyde Park, New York, United States, 11040
- Research site
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Research site
-
-
Ohio
-
Centerville, Ohio, United States, 45459
- Research site
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73112
- Research site
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Research site
-
-
Tennessee
-
Johnson City, Tennessee, United States, 37614
- Research site
-
-
Vermont
-
Bennington, Vermont, United States, 05201
- Research site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria (autopsy cohort):
- Have a projected life expectancy of ≤ 6 months as determined by the principal investigator (e.g. terminal medical condition) or are already enrolled in a longitudinal study of aging with an autopsy component;
- Can tolerate a 10 minute PET scan; and
- Give informed consent for study procedures and brain donation consistent with the legal requirements of the State in which they are enrolled and the State in which they die.
Inclusion Criteria (specificity cohort):
- Cognitively and neurologically healthy males and females 18 to 40 years of age;
- Who had no known risk factors for AD, including:
- Known genetic risk factors for AD, including an ApoE ε4 allele (note: ApoE genotype was determined after enrollment and was not disclosed to healthy control subjects). Scans from subjects carrying an ApoE ε4 allele were not included in the primary specificity analysis, but were included in an exploratory analysis;
- First degree relative with a known progressive dementing disorder;
- History of cognitive decline;
- History of neurologic, neurodegenerative, or psychiatric disease;
- History of head trauma; or
- Evidence of brain abnormality on a MRI scan;
- Who performed in an age-appropriate normal range on the Wechsler Logical Memory I & II, story A;
- Who could tolerate a 10-minute PET scan; and
- Who provided informed consent before any study procedures were performed.
Exclusion Criteria:
- Have primary brain tumor, known metastases to the brain, central nervous system (CNS) lymphoma;
- Have any major, focal structural loss of brain matter;
- Are aggressively being treated with life sustaining measures (e.g. currently on respirator; receiving high dose chemotherapy);
- Have a clinically significant infectious disease, including Acquired Immune Deficiency Syndrome (AIDS), Human Immunodeficiency Virus (HIV) infection, previous positive test for hepatitis or HIV or Creutzfeldt-Jakob disease (CJD);
- Are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days;
- Have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, secretase inhibitor);
- Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session; or
- Are females of childbearing potential who are pregnant or not using adequate contraception.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Autopsy Cohort
End-of-life subjects (life expectancy < 6 months) consenting to brain donation at autopsy.
|
Single i.v.
bolus injection of 370MBq (10 mCi) followed by saline flush, 50 minutes prior to imaging, 10 minute image duration
Other Names:
|
Experimental: Specificity Cohort
Younger healthy controls presumed to be devoid of beta-amyloid plaques.
|
Single i.v.
bolus injection of 370MBq (10 mCi) followed by saline flush, 50 minutes prior to imaging, 10 minute image duration
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation of Florbetapir-PET Image and Amyloid Plaque Density
Time Frame: at autopsy up to 12 months post-scan
|
Spearman's rank order correlation of the median semi-quantitative visual read of the florbetapir-PET image and the amyloid plaque density assessed post-mortem by quantitative immunohistochemistry (IHC) averaged across 6 brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate).
Spearman's rank order correlation ranges from -1 to +1.
A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
|
at autopsy up to 12 months post-scan
|
Specificity Analysis
Time Frame: 50-60 min after injection
|
Specificity of florbetapir-PET scan in younger healthy controls presumed to be negative for amyloid.
Specificity results are reported as the number of subjects who had a negative scan based on majority of 3 blinded readers.
|
50-60 min after injection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Regional Correlation Analysis
Time Frame: at autopsy up to 12 months post-scan
|
Spearman's rank order correlation of median visual read of the florbetapir-PET image vs. amyloid plaque density assessed post-mortem by quantitative IHC of six individual brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate).
Spearman's rank order correlation ranges from -1 to +1.
A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
|
at autopsy up to 12 months post-scan
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012 Aug;11(8):669-78. doi: 10.1016/S1474-4422(12)70142-4. Epub 2012 Jun 28. Erratum In: Lancet Neurol. 2012 Aug;11(8):658.
- Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML, Krautkramer MJ, Kung HF, Coleman RE, Doraiswamy PM, Fleisher AS, Sabbagh MN, Sadowsky CH, Reiman EP, Zehntner SP, Skovronsky DM; AV45-A07 Study Group. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011 Jan 19;305(3):275-83. doi: 10.1001/jama.2010.2008. Erratum In: JAMA. 2011 Mar 16;305(11):1096. Reiman, P Eric M [corrected to Reiman, Eric M].
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18F-AV-45-A07
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Alzheimer's Disease
-
University of Southern CaliforniaAlzheimer's Therapeutic Research Institute; American Heart Association; Schaeffer...RecruitingDementia | Alzheimer Disease | Prodromal Alzheimer's Disease | Preclinical Alzheimer's DiseaseUnited States
-
University of Southern CaliforniaNational Institute on Aging (NIA); Alzheimer's Therapeutic Research Institute; Brigham and Women's Hospital and other collaboratorsActive, not recruitingDementia | Alzheimer Disease | Prodromal Alzheimer's Disease | Preclinical Alzheimer's DiseaseUnited States
-
Novoic LimitedRecruitingAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's DiseaseUnited States
-
Novoic LimitedRecruitingAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's DiseaseUnited Kingdom
-
Novoic LimitedCompletedAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's DiseaseUnited States
-
Novoic LimitedCompletedAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's DiseaseUnited Kingdom
-
Novoic LimitedRecruitingAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's DiseaseUnited Kingdom
-
Novoic LimitedRecruitingAlzheimer Disease | Mild Cognitive Impairment | Prodromal Alzheimer's Disease | Alzheimer's Disease (Incl Subtypes) | Preclinical Alzheimer's Disease | Normal CognitionUnited States
-
University Hospital, BordeauxMinistry for Health and Solidarity, FranceCompletedAlzheimer's Disease (AD) | Alzheimer's Disease (AD) Related DisordersFrance
-
University of Colorado, DenverNational Institute on Aging (NIA)Active, not recruitingSuspected Typical Alzheimer's Disease (AD) | Suspected Atypical Alzheimer's Disease (AD)United States
Clinical Trials on florbetapir F 18
-
Brigham and Women's HospitalTerminatedCardiac AmyloidosisUnited States
-
Avid RadiopharmaceuticalsWithdrawnAlzheimer's DiseaseJapan
-
Avid RadiopharmaceuticalsCompletedProgressive Cognitive DeclineUnited States
-
Avid RadiopharmaceuticalsNational Institute of Neurological Disorders and Stroke (NINDS); National Institutes...CompletedParkinson's DiseaseUnited States
-
Avid RadiopharmaceuticalsCompletedAlzheimer DiseaseUnited States
-
Avid RadiopharmaceuticalsCompletedAlzheimer's Disease
-
Avid RadiopharmaceuticalsCompletedMild Cognitive Impairment | Alzheimer's DiseaseUnited States
-
Chang Gung Memorial HospitalUnknown
-
Avid RadiopharmaceuticalsCompletedNeurodegenerative Diseases | Alzheimer Disease | Mild Cognitive Impairment
-
Avid RadiopharmaceuticalsCompletedAlzheimer's Disease