Alzheimer's DiseaseEarly Phase 111C-PIB PETNCT00811122
Biodistribution of 11C-PIB PET in Alzheimer's Disease, Frontotemporal Dementia, and Cognitively Normal Elderly
A Early Phase 1 study testing 11C-PIB PET Scan and FDG-PET Scan in people with Alzheimer's Disease, run by University of Utah at 1 site in United States.
Trial summary
Alzheimer's disease (AD) is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss. Amyloid plaques are believed to play an integral role in AD. Elevated levels of Aβ in the brain are correlated with cognitive decline. There are no approved ways to measure amyloid load in humans. Read more about this study
- Who is it for?
- Ages 30 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- 11C-PIB PET Scan and FDG-PET Scan
- Type of treatment
- Surgery or procedure
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Dec 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 30 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All participants will be between 30-90 years old, inclusive, clinically characterized as having AD, having FTD, or being cognitively normal controls (NC).
- All subjects must be willing and able to undergo testing procedures.
- Cholinesterase inhibitors and memantine - symptomatic drugs approved for AD - will be allowed since these drugs are not expected to significantly affect amyloid load.
- General inclusion criteria are shown below:
- Normal subjects: Healthy individuals aged to match AD and FTD groups, who are non-depressed, non-demented, and without a complaint of memory loss. A brief neuropsychological test, the 3MS-R or Modified Mini-Mental State Examination, Revised (Tschanz et al., 2002), will be given to confirm that the subject is not cognitively impaired.
- FTD subjects: Patients seen in the University of Utah (UU) Cognitive Disorders Clinic (CDC) who have been clinically characterized and meet Neary criteria for frontotemporal dementia (Neary et al., 1998).
- AD subjects: Patients seen in the UU CDC who have been clinically characterized to meet NINCDS-ADRDA criteria for probable AD (McKhann et al., 1984). These criteria were established in 1984 for diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).
Who cannot join
- Subjects with medical conditions that have a high risk of associated cognitive symptoms such as transient ischemic attack (TIA), stroke, seizures, or head injury with loss of consciousness within five years
- Subjects with Axis I psychiatric diagnoses other than treated depression
- Subjects who are not medically stable will be excluded from the study. Examples of medically unstable patients include uncontrolled hypertension, heart/liver/renal failure, and other conditions requiring acute medical attention
- Subjects cannot have a serum glucose level greater than 180 mg/dl for FDG-PET imaging
- Subjects who are too claustrophobic to undergo FDG-PET or 11C PIB-PET imaging
- Subjects who require conscious sedation or anesthesia to undergo FDG-PET or 11C PIB-PET imaging
- Subjects who are unable to follow instructions to urinate after completing scanning procedures
Trial locations and contacts
1 site in 1 country.
About this study
Alzheimer's disease (AD) is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss. Amyloid plaques are believed to play an integral role in AD. Elevated levels of Aβ in the brain are correlated with cognitive decline.
There are no approved ways to measure amyloid load in humans. Several compounds are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. The most promising compound is 11C-PIB, or Pittsburgh Compound-B. This compound can be injected and a PET scan performed. This allows doctors to see the amyloid plaques in the brain, and to use this information to look at other types of dementia to see if there are differences and/or similarities in the plaques.
Read more
We will recruit a total of 30 subjects, 10 from each of the following three diagnostic categories: frontotemporal dementia (FTD), Alzheimer's disease, and normal volunteers. All subjects will be given an [18F]fluorodeoxyglucose or FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.
The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups.
Read the detailed description
Biomarkers of Alzheimer's disease (AD) have recently become extremely important for a number of reasons: to improve diagnosis, to measure severity of disease, to measure progression of disease, to measure effects of novel disease-modifying drugs and to speed development of these novel experimental drugs by reducing time needed to follow patients, number of patients to be followed per study, and cost of research. (Thal, 2006, Nichols, 2006)
The neuropathology of AD is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss (Braak and Braak, 1997). Amyloid plaques are believed to play an integral role in AD (Selkoe, 1993). Plaques are neurotoxic (Yankner, 1989). Elevated levels of Aβ in the brain are correlated with cognitive decline (Naslund, 2000). Removal of plaques in animal models of AD results in behavioral improvements (Arendash, 2001).
There are no approved in vivo markers of amyloid load in humans. Several compounds with affinity for binding amyloid in vivo are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. Attempts at finding non-radioactive amyloid tracers are underway, but still poorly developed. The most promising compound is 11C-PIB. Pittsburgh Compound-B has statistically significant increased retention in AD cortical areas, relative to controls (P<0.05). (Price, 2005) To our knowledge, 11C-PIB imaging has not been compared against frontotemporal dementia (FTD) controls.
We will recruit (from our clinic population), a total of 30 subjects, 10 from each of the following 3 diagnostic categories: frontotemporal dementia, Alzheimer's disease, and normal volunteers. All subjects will be given an FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.
Objective and Hypothesis:
The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups. Comparison with FDG-PET is essential to confirm group membership and for anatomic co-registration of 11C-PIB images.
Specific Aim 1: Determine the biodistribution of 11C-PIB in AD, FTD, and cognitively normal elderly individuals and determine whether it reflects the distribution of amyloid plaques in the brain expected from postmortem studies.
Hypothesis 1: The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals.
Hypothesis 2: Patients with AD scanned with 11C-PIB will have higher standardized uptake values (SUVs) than cognitively normal elderly in brain regions where beta amyloid are expected to be over-expressed.
Hypothesis 3: Patients with FTD scanned with 11C-PIB will have similar standardized uptake values (SUVs) as cognitively normal elderly subjects and lower values than in AD subjects in brain regions where beta amyloid are expected in AD to be overexpressed.
Specific Aim 2: Correlate glucose metabolism with 11C-PIB PET results.
Hypothesis 4: Patients with a pattern of glucose hypometabolism suggestive of FTD with FDG-PET have 11C-PIB uptake and brain biodistribution similar to cognitively normal elderly, while those with a pattern of glucose hypometabolism suggestive of AD have abnormal PIB uptake and brain biodistribution of 11C-PIB
- Conditions
- Alzheimer's Disease
- Being tested
- 11C-PIB PET Scan, FDG-PET Scan
- Keywords
- Alzheimer's disease, AD, Frontotemporal dementia, FTD
- Medical subject headings
- Alzheimer Disease, Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-PIB PET ScanRadiation
Also called 11 Carbon Pittsburgh compound B
Participants will receive an 11C-PIB PET scan of the brain.
FDG-PET ScanRadiation
Also called 2-deoxy-2-[18F]fluoro-D-glucose (FDG)
Participants will receive an FDG-PET scan of the brain.
What is being measured
The primary outcome is the main question the study is designed to answer.
The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals.
Measured: 4 months
Secondary outcomes (1)
Patients with AD scanned with 11C-PIB will have higher standardized uptake values (SUVs) than cognitively normal elderly in brain regions where beta amyloid are expected to be over-expressed.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2008 (estimated)
- Study startNov 2009
- Primary completionDec 2021
- Study completionDec 2021
Why it stopped: A Fluorine-18 labeled version of the radiopharmaceutical (Flutemetamol) became available. This version is far superior to the Carbon-11 PiB. There is no need to make this compound available any longer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John M Hoffman, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811122
- Sponsor's protocol ID
- 17991
- Acronym
- 11C-PIB PET
- Status last verified
- Jun 2020
- First submitted
- 16 Dec 2008
- Last updated
- 24 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biodistribution of 11C-PIB PET in Alzheimer's Disease, Frontotemporal Dementia, and Cognitively Normal Elderly
- ClinicalTrials.gov ID
- NCT00811122
- Acronym / sponsor ID
- 11C-PIB PET / 17991
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, AD, Frontotemporal dementia, FTD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A Fluorine-18 labeled version of the radiopharmaceutical (Flutemetamol) became available. This version is far superior to the Carbon-11 PiB. There is no need to make this compound available any longer.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Nov 2009 (actual)
- Primary completion
- Dec 2021 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 18 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alzheimer's disease (AD) is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss. Amyloid plaques are believed to play an integral role in AD. Elevated levels of Aβ in the brain are correlated with cognitive decline.
There are no approved ways to measure amyloid load in humans. Several compounds are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. The most promising compound is 11C-PIB, or Pittsburgh Compound-B. This compound can be injected and a PET scan performed. This allows doctors to see the amyloid plaques in the brain, and to use this information to look at other types of dementia to see if there are differences and/or similarities in the plaques.
We will recruit a total of 30 subjects, 10 from each of the following three diagnostic categories: frontotemporal dementia (FTD), Alzheimer's disease, and normal volunteers. All subjects will be given an [18F]fluorodeoxyglucose or FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.
The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups.
Detailed description
Biomarkers of Alzheimer's disease (AD) have recently become extremely important for a number of reasons: to improve diagnosis, to measure severity of disease, to measure progression of disease, to measure effects of novel disease-modifying drugs and to speed development of these novel experimental drugs by reducing time needed to follow patients, number of patients to be followed per study, and cost of research. (Thal, 2006, Nichols, 2006)
The neuropathology of AD is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss (Braak and Braak, 1997). Amyloid plaques are believed to play an integral role in AD (Selkoe, 1993). Plaques are neurotoxic (Yankner, 1989). Elevated levels of Aβ in the brain are correlated with cognitive decline (Naslund, 2000). Removal of plaques in animal models of AD results in behavioral improvements (Arendash, 2001).
There are no approved in vivo markers of amyloid load in humans. Several compounds with affinity for binding amyloid in vivo are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. Attempts at finding non-radioactive amyloid tracers are underway, but still poorly developed. The most promising compound is 11C-PIB. Pittsburgh Compound-B has statistically significant increased retention in AD cortical areas, relative to controls (P<0.05). (Price, 2005) To our knowledge, 11C-PIB imaging has not been compared against frontotemporal dementia (FTD) controls.
We will recruit (from our clinic population), a total of 30 subjects, 10 from each of the following 3 diagnostic categories: frontotemporal dementia, Alzheimer's disease, and normal volunteers. All subjects will be given an FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.
Objective and Hypothesis:
The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups. Comparison with FDG-PET is essential to confirm group membership and for anatomic co-registration of 11C-PIB images.
Specific Aim 1: Determine the biodistribution of 11C-PIB in AD, FTD, and cognitively normal elderly individuals and determine whether it reflects the distribution of amyloid plaques in the brain expected from postmortem studies.
Hypothesis 1: The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals.
Hypothesis 2: Patients with AD scanned with 11C-PIB will have higher standardized uptake values (SUVs) than cognitively normal elderly in brain regions where beta amyloid are expected to be over-expressed.
Hypothesis 3: Patients with FTD scanned with 11C-PIB will have similar standardized uptake values (SUVs) as cognitively normal elderly subjects and lower values than in AD subjects in brain regions where beta amyloid are expected in AD to be overexpressed.
Specific Aim 2: Correlate glucose metabolism with 11C-PIB PET results.
Hypothesis 4: Patients with a pattern of glucose hypometabolism suggestive of FTD with FDG-PET have 11C-PIB uptake and brain biodistribution similar to cognitively normal elderly, while those with a pattern of glucose hypometabolism suggestive of AD have abnormal PIB uptake and brain biodistribution of 11C-PIB
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- All participants will be between 30-90 years old, inclusive, clinically characterized as having AD, having FTD, or being cognitively normal controls (NC).
- All subjects must be willing and able to undergo testing procedures.
- Cholinesterase inhibitors and memantine - symptomatic drugs approved for AD - will be allowed since these drugs are not expected to significantly affect amyloid load.
- Normal subjects: Healthy individuals aged to match AD and FTD groups, who are non-depressed, non-demented, and without a complaint of memory loss. A brief neuropsychological test, the 3MS-R or Modified Mini-Mental State Examination, Revised (Tschanz et al., 2002), will be given to confirm that the subject is not cognitively impaired.
- FTD subjects: Patients seen in the University of Utah (UU) Cognitive Disorders Clinic (CDC) who have been clinically characterized and meet Neary criteria for frontotemporal dementia (Neary et al., 1998).
Key exclusion criteria (7 listed)
- Subjects with medical conditions that have a high risk of associated cognitive symptoms such as transient ischemic attack (TIA), stroke, seizures, or head injury with loss of consciousness within five years
- Subjects with Axis I psychiatric diagnoses other than treated depression
- Subjects who are not medically stable will be excluded from the study. Examples of medically unstable patients include uncontrolled hypertension, heart/liver/renal failure, and other conditions requiring acute medical attention
- Subjects cannot have a serum glucose level greater than 180 mg/dl for FDG-PET imaging
- Subjects who are too claustrophobic to undergo FDG-PET or 11C PIB-PET imaging
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 |
|---|---|---|
| 11C-PIB PET ScanAlso: 11 Carbon Pittsburgh compound BParticipants will receive an 11C-PIB PET scan of the brain. | Radiation | – |
| FDG-PET ScanAlso: 2-deoxy-2-[18F]fluoro-D-glucose (FDG)Participants will receive an FDG-PET scan of the brain. | Radiation | – |
Primary outcome
The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals.
Time frame: 4 months
1 secondary outcome
Patients with AD scanned with 11C-PIB will have higher standardized uptake values (SUVs) than cognitively normal elderly in brain regions where beta amyloid are expected to be over-expressed.
Time frame: 4 months
Results and safety
The study was stopped early (reason given: A Fluorine-18 labeled version of the radiopharmaceutical (Flutemetamol) became available. This version is far superior to the Carbon-11 PiB. There is no need to make this compound available any longer.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2023.
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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.
John M Hoffman, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 11C-PIB PET Scan and FDG-PET Scan in people with Alzheimer's Disease, run by University of Utah at 1 site 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 7 inclusion and 7 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: stopped early, as of the sponsor's last update on 24 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: A Fluorine-18 labeled version of the radiopharmaceutical (Flutemetamol) became available. This version is far superior to the Carbon-11 PiB. There is no need to make this compound available any longer.). Results are not available in the source record.
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?
The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Apr 2023.