Alzheimer's DiseasePhase 3NCT00857415
Phase III Study of the Correlation Between Florbetapir F18 PET Imaging and Amyloid Pathology in the Brain
A Phase 3 study testing florbetapir F 18 in people with Alzheimer's Disease, run by Avid Radiopharmaceuticals at 25 sites in United States.
Trial summary
The study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid by dissection of the brain at autopsy. Amyloid in the brain is a key feature of Alzheimer's Disease (AD). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- florbetapir F 18
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 226 participants
- Where
- 25 sitesUnited States
- Study dates
- Dec 2008to May 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- 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;
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- 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.
Who cannot join
- 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.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Research Site
Albany, New York, 12208
Research Site
Baltimore, Maryland, 21221
Research Site
Bennington, Vermont, 05201
Research Site
Centerville, Ohio, 45459
Research Site
Charleston, South Carolina, 29425
Research Site
Durham, North Carolina, 27710
Research Site
Fort Myers, Florida, 33912
Research Site
Hattiesburg, Mississippi, 39401
Research Site
Irvine, California, 92697
Research Site
Johnson City, Tennessee, 37614
Research Site
Little Rock, Arkansas, 72211
Research Site
Miami, Florida, 33137
Research Site
Miami Beach, Florida, 33140
Research Site
Miami Springs, Florida, 33166
Research Site
New Hyde Park, New York, 11040
Research Site
Oklahoma City, Oklahoma, 73112
Research Site
Orlando, Florida, 32835
Research Site
Phoenix, Arizona, 85006
Research Site
San Francisco, California, 94109
Research Site
Sarasota, Florida, 34231
Research Site
Scottsdale, Arizona, 85258
Research Site
St Louis, Missouri, 63141
Research Site
St. Petersburg, Florida, 33709
Research Site
Sun City, Arizona, 85351
Research Site
West Palm Beach, Florida, 33407
About this study
Official title: A Phase III Study of the Correlation Between Florbetapir F 18 (18F-AV-45) PET Imaging and Amyloid Pathology
The study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid by dissection of the brain at autopsy. Amyloid in the brain is a key feature of Alzheimer's Disease (AD).
Read the 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.
- Conditions
- Alzheimer's Disease
- Being tested
- florbetapir F 18
- Keywords
- florbetapir F 18 PET, amyloid imaging, Amyloid pathology in the brain
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
florbetapir F 18Drug
Also called 18F-AV-45, AV-45, Amyvid
Single i.v. bolus injection of 370MBq (10 mCi) followed by saline flush, 50 minutes prior to imaging, 10 minute image duration
| Study group | Role | What they receive |
|---|---|---|
| Autopsy Cohort | Experimental | End-of-life subjects (life expectancy < 6 months) consenting to brain donation at autopsy. Receives: Drug: florbetapir F 18 |
| Specificity Cohort | Experimental | Younger healthy controls presumed to be devoid of beta-amyloid plaques. Receives: Drug: florbetapir F 18 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of Florbetapir-PET Image and Amyloid Plaque Density
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.
Measured: at autopsy up to 12 months post-scan
Specificity Analysis
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.
Measured: 50-60 min after injection
Secondary outcomes (1)
Regional Correlation Analysis
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.
Measured: at autopsy up to 12 months post-scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study startDec 2008
- Primary completionMar 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- Avid Radiopharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Avid Radiopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857415
- Sponsor's protocol ID
- 18F-AV-45-A07
- Status last verified
- May 2012
- First submitted
- 5 Mar 2009
- Last updated
- 22 May 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21245183Clark 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.
PubMed 22749065
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study of the Correlation Between Florbetapir F 18 (18F-AV-45) PET Imaging and Amyloid Pathology
- ClinicalTrials.gov ID
- NCT00857415
- Acronym / sponsor ID
- 18F-AV-45-A07
- Conditions
- Alzheimer's Disease
- Keywords
- florbetapir F 18 PET, amyloid imaging, Amyloid pathology in the brain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- Avid RadiopharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Posted 7 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid by dissection of the brain at autopsy. Amyloid in the brain is a key feature of Alzheimer's Disease (AD).
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Autopsy Cohort | Experimental | Drug: florbetapir F 18End-of-life subjects (life expectancy < 6 months) consenting to brain donation at autopsy. |
| Specificity Cohort | Experimental | Drug: florbetapir F 18Younger healthy controls presumed to be devoid of beta-amyloid plaques. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- Cognitively and neurologically healthy males and females 18 to 40 years of age;
- Who had no known risk factors for AD, including:
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| florbetapir F 18Also: 18F-AV-45, AV-45, AmyvidSingle i.v. bolus injection of 370MBq (10 mCi) followed by saline flush, 50 minutes prior to imaging, 10 minute image duration | Drug | Autopsy Cohort, Specificity Cohort |
Primary outcome
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.
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.
1 secondary outcome
Regional Correlation Analysis
Time frame: at autopsy up to 12 months post-scan
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21245183Clark 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.
- Derived from this study: PubMed 22749065Clark 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer study director
Avid Radiopharmaceuticals
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing florbetapir F 18 in people with Alzheimer's Disease, run by Avid Radiopharmaceuticals at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of Florbetapir-PET Image and Amyloid Plaque Density (time frame: at autopsy up to 12 months post-scan). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00857415, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2012.