Atypical Alzheimers DiseasePhase 1NCT01723553
Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD
A Phase 1 study testing C-11 PiB in people with Atypical Alzheimers Disease and Logopenic Variant of Primary Progressive Aphasia (LPA), run by Mayo Clinic at 1 site in United States.
Trial summary
The study is designed to assess the demographic, clinical and imaging associations with the presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that cognitive and functional performance will be poorer in atypical Alzheimer's subjects with microbleeds compared to those without microbleeds. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atypical Alzheimers Disease, Logopenic Variant of Primary Progressive Aphasia (LPA), Posterior Cortical Atrophy (PCA)
- What is being tested?
- C-11 PiB
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to Mar 2015
- Phase
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- over the age of 21
- will have an informant/study partner who will be able to provide independent evaluation of functioning
- must fulfill clinical diagnostic criteria for atypical AD, and hence should either have a chief complaint of difficulty with language and fulfill criteria for logopenic variant of primary progressive aphasia, or present with visuospatial/perceptual deficits and fulfill criteria for posterior cortical atrophy
- speaks English as their primary language (including bilingual patients whose primary language is English)
- agrees to and is eligible to undergo MRI and PET scanning
- if woman of child bearing age, must agree to pregnancy test no more than 48 hours before the PET scans
Who cannot join
- subjects with concurrent illnesses that could account for the presenting syndrome, such as traumatic brain injury, strokes or developmental syndromes
- subjects meeting criteria for another neurodegenerative disease, particularly typical Alzheimer's dementia
- women that are pregnant or post-partum and breast-feeding
- subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, and if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm)
- subjects will also be excluded if they do not have an informant, do not consent to research or do not complete all components of the study (neurological exam, neuropsychometric tests, MRI, PiB PET)
Trial locations and contacts
1 site in 1 country.
About this study
The study is designed to assess the demographic, clinical and imaging associations with the presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that cognitive and functional performance will be poorer in atypical Alzheimer's subjects with microbleeds compared to those without microbleeds.
Read the detailed description
Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA). Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a consequence of leakage of blood products out of vessels that have been damaged by deposition of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it is also possible that cerebrovascular disease could contribute to the presence of MBs in AD. Subjects with MBs are at a greater risk of bleeds which could impact the use of anti-coagulation treatment approaches.
The presence of CAA has been particularly associated with AD and studies have demonstrated that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large proportion of subjects showing multiple MBs. The presence of MBs has been associated with older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests cerebrovascular disease may also play a role in the etiology of MBs in AD. However, approximately 16% of AD subjects do not present with episodic memory loss, but instead display language problems such as poor naming and impaired sentence repetition, or visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical AD, although no studies have assessed MBs in atypical AD.
Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET scanning have now been developed and provide an invaluable biomarker to infer the presence of β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and hence the assessment of PiB-PET in subjects with MBs will provide important information on the association of MBs and β-amyloid deposition in AD.
The goal of the study is to assess the associations between MBs and demographic/clinical features, assess the associations between MBs and imaging features as well as a possible correlate to the number of MBs a subject has in atypical AD.
Patients found to be eligible and willing to enroll in this study will be asked to undergo a Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the brain. This will be done over a period of two days at the Mayo Clinic in Rochester, Minnesota.
- Conditions
- Atypical Alzheimers Disease, Logopenic Variant of Primary Progressive Aphasia (LPA), Posterior Cortical Atrophy (PCA)
- Being tested
- C-11 PiB
- Keywords
- aphasia, logopenic, PCA, LPA
- Medical subject headings
- Aphasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C-11 PiBDrug
Also called Pittsburgh Compound B, PiB
One time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).
| Study group | Role | What they receive |
|---|---|---|
| PiB positron emission tomography (PET) | Experimental | All subjects will receive PET imaging with C-11 PiB on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains. Receives: Drug: C-11 PiB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with and without microbleeds
Measured: up to day 2 of study
Secondary outcomes (2)
Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan
Measured: Study entry, approximately day 1 or day 2 of study
Number of microbleeds per subject
Measured: Study entry, approximately day 1 or day 2 of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Alzheimers DiseaseStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Whitwell, Mayo Clinic
- Investigators
- Jennifer Whitwell, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723553
- Sponsor's protocol ID
- 12-007139
- Status last verified
- Dec 2015
- First submitted
- 6 Nov 2012
- Last updated
- 21 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD
- ClinicalTrials.gov ID
- NCT01723553
- Acronym / sponsor ID
- 12-007139
- Conditions
- Atypical Alzheimers Disease, Logopenic Variant of Primary Progressive Aphasia (LPA), Posterior Cortical Atrophy (PCA)
- Keywords
- aphasia, logopenic, PCA, LPA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 8 Nov 2012 (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.
The study is designed to assess the demographic, clinical and imaging associations with the presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that cognitive and functional performance will be poorer in atypical Alzheimer's subjects with microbleeds compared to those without microbleeds.
Detailed description
Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA). Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a consequence of leakage of blood products out of vessels that have been damaged by deposition of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it is also possible that cerebrovascular disease could contribute to the presence of MBs in AD. Subjects with MBs are at a greater risk of bleeds which could impact the use of anti-coagulation treatment approaches.
The presence of CAA has been particularly associated with AD and studies have demonstrated that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large proportion of subjects showing multiple MBs. The presence of MBs has been associated with older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests cerebrovascular disease may also play a role in the etiology of MBs in AD. However, approximately 16% of AD subjects do not present with episodic memory loss, but instead display language problems such as poor naming and impaired sentence repetition, or visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical AD, although no studies have assessed MBs in atypical AD.
Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET scanning have now been developed and provide an invaluable biomarker to infer the presence of β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and hence the assessment of PiB-PET in subjects with MBs will provide important information on the association of MBs and β-amyloid deposition in AD.
The goal of the study is to assess the associations between MBs and demographic/clinical features, assess the associations between MBs and imaging features as well as a possible correlate to the number of MBs a subject has in atypical AD.
Patients found to be eligible and willing to enroll in this study will be asked to undergo a Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the brain. This will be done over a period of two days at the Mayo Clinic in Rochester, Minnesota.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PiB positron emission tomography (PET) | Experimental | Drug: C-11 PiBAll subjects will receive PET imaging with C-11 PiB on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- over the age of 21
- will have an informant/study partner who will be able to provide independent evaluation of functioning
- must fulfill clinical diagnostic criteria for atypical AD, and hence should either have a chief complaint of difficulty with language and fulfill criteria for logopenic variant of primary progressive aphasia, or present with visuospatial/perceptual deficits and fulfill criteria for posterior cortical atrophy
- speaks English as their primary language (including bilingual patients whose primary language is English)
- agrees to and is eligible to undergo MRI and PET scanning
Key exclusion criteria (5 listed)
- subjects with concurrent illnesses that could account for the presenting syndrome, such as traumatic brain injury, strokes or developmental syndromes
- subjects meeting criteria for another neurodegenerative disease, particularly typical Alzheimer's dementia
- women that are pregnant or post-partum and breast-feeding
- subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, and if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm)
- subjects will also be excluded if they do not have an informant, do not consent to research or do not complete all components of the study (neurological exam, neuropsychometric tests, MRI, PiB PET)
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 |
|---|---|---|
| C-11 PiBAlso: Pittsburgh Compound B, PiBOne time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq). | Drug | PiB positron emission tomography (PET) |
Primary outcome
Proportion of subjects with and without microbleeds
Time frame: up to day 2 of study
2 secondary outcomes
Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan
Time frame: Study entry, approximately day 1 or day 2 of study
Number of microbleeds per subject
Time frame: Study entry, approximately day 1 or day 2 of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2015.
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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.
Jennifer Whitwell, PhD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing C-11 PiB in people with Atypical Alzheimers Disease and Logopenic Variant of Primary Progressive Aphasia (LPA), run by Mayo Clinic 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 6 inclusion and 5 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 21 Dec 2015. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of subjects with and without microbleeds (time frame: up to day 2 of study). 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 21 Dec 2015.