Alzheimer DiseaseNCT03075007
Brain Vascular Disease in Aging and Dementia
An observational study of Alzheimer Disease and White Matter Hyperintensities, run by Columbia University at 1 site in United States.
Trial summary
This study examines the factors that may drive the relationship between vascular disease and Alzheimer's Disease (AD) in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, White Matter Hyperintensities, Dementia
- What is being tested?
- Florbetaben F18 and Transcranial Doppler
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 23 May 2017to 31 Aug 2019
- Phase
- Observational
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Potential participants are recruited from a list of active members in the Washington Heights/Hamilton Heights/ Inwood Columbia Aging Project, known as WHICAP (CU IRB# AAAO9804), who previously completed a repeat MRI as part of a neuroimaging sub-study (IRB# AAAO9758). Some participants (n=30) will already have had baseline amyloid PET imaging under PI IRB protocol # 7130R (BAY 949172PET/CT in Older Adults).
Who may be able to join
- current participant in WHICAP (Washington Heights/Inwood Columbia Aging Project)
- subject previously participated in baseline MRI sub-study
- post-menopausal
Who cannot join
- allergic to Florbetaben
- claustrophobic
- liver problems
- history of epilepsy/seizures
- pre-menopausal
- serious medical conditions
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: White Matter Hyperintensities in Aging and Dementia
This study examines the factors that may drive the relationship between vascular disease and Alzheimer's Disease (AD) in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. In past research, the investigators demonstrated that accumulation of brain vascular disease is associated with risk for development of AD. The study now extends the research to examine how brain vascular disease and AD interact. In this pilot study, the investigators will obtain positron emission tomography (PET) scans to measure amyloid (one of the protein pathological markers of AD) from participants in an ongoing community-based study of aging and dementia (WHICAP). The study will include subjects who are already enrolled in the parent project. Further, this study will enroll both subjects who have never been evaluated with PET scans and those who received a previous baseline PET scan. The study plans to obtain approximately 30 repeat amyloid PET scans and 20 baseline PET scans. The investigators will also conduct transcranial Doppler studies to measure blood flow in the participants with amyloid PET scans. The potential benefits to society should be considerable if this study reveals new information about risk factors for or contributions to AD.
Read the detailed description
Alzheimer's disease (AD) is one of the most devastating international public health epidemics. There are currently no effective disease-modifying or preventative strategies. Current pathogenic models emphasize a single pathway of disease pathogenesis, but underestimate the contribution of small vessel cerebrovascular disease, which manifests primarily as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). Understanding of the factors that drive the relationship between vascular disease and AD remains elusive; vascular factors may be independent sources of dysfunction that contribute additively to clinical expression, they may interact mechanistically with AD pathology, and/or they may relate to each other because of a shared association with a third set of factors. These issues are particularly relevant among ethnic/racial minorities, who are at much greater risk for clinical AD, have more severe cerebrovascular disease, but appear to have similar levels of AD pathology compared with Whites.
The proposed research examines these factors in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. The investigators demonstrated that accumulation of WMH, particularly in parietal lobes, predicts incident AD, and is associated with the presence of cerebral microbleeds, an indicator of cerebral amyloid angiopathy. The investigators extend the research to examine mechanistic interactions between cerebrovascular disease and AD. The preliminary data suggest that individuals with evidence of fibrillar amyloidosis have increased parietal lobe WMH and that hemodynamic markers of autoregulatory dysfunction are associated with both WMH and amyloid deposition, which in turn interact to promote the clinical expression of AD. These findings are buffered by new data that establish WMH as a core feature in autosomal dominant forms of AD. In this pilot study, the investigators propose to obtain cross-sectional and longitudinal MRI and amyloid PET data from participants in WHICAP.
- Conditions
- Alzheimer Disease, White Matter Hyperintensities, Dementia, Aging
- Being tested
- Florbetaben F18, Transcranial Doppler
- Keywords
- Alzheimer Disease, Aging, Dementia, PET
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Florbetaben F18Radiation
10Meq of Florbetaben F 18 via intravenous injection is to be used. Visit duration is approximately 3 hours.
Transcranial DopplerProcedure or surgery
All participants will undergo Doppler ultrasonography that measures the velocity of blood flow through the brain's blood vessels. Visit duration is approximately 45 minutes and will be scheduled for either the same day or another day as the PET scan.
| Study group | Role | What they receive |
|---|---|---|
| Group A | All participants will undergo an amyloid PET scan with Florbetaben F 18 contrast as well as a transcranial Doppler ultrasound. Receives: Radiation: Florbetaben F18; Procedure: Transcranial Doppler |
What is being measured
The primary outcome is the main question the study is designed to answer.
PET amyloid Standard Uptake Value ratio (SUVr) values
The primary outcome is the mean standard uptake value ratio in the 4 regions of interest.
Measured: up to 18 months
Transcranial Doppler (TCD) dynamic autoregulatory dysfunction
Cerebral blood flow velocities (CBFV) are assessed using TCD. Arterial blood pressure (ABP) is recorded simultaneously using the Finapres on the middle phalanx of the left or right middle finger. The phase shift between the two streaming signals is an indication of the extent to which oscillations in CBFV lead those in ABP and can be interpreted as active early counter-regulation. Lower phase shift reflects increased latency in cerebral vasomotion and thus poorer autoregulation.
Measured: up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start23 May 2017
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Adam Brickman, Columbia University
- Investigators
- Adam M Brickman, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03075007
- Sponsor's protocol ID
- AAAR1423
- Other IDs
- 2R56AG034189-06A1
- Status last verified
- Sep 2019
- First submitted
- 6 Mar 2017
- Last updated
- 12 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- White Matter Hyperintensities in Aging and Dementia
- ClinicalTrials.gov ID
- NCT03075007
- Acronym / sponsor ID
- AAAR1423
- Conditions
- Alzheimer Disease, White Matter Hyperintensities, Dementia, Aging
- Keywords
- Alzheimer Disease, Aging, Dementia, PET
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 23 May 2017 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 9 Mar 2017 (actual)
- 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.
This study examines the factors that may drive the relationship between vascular disease and Alzheimer's Disease (AD) in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. In past research, the investigators demonstrated that accumulation of brain vascular disease is associated with risk for development of AD. The study now extends the research to examine how brain vascular disease and AD interact. In this pilot study, the investigators will obtain positron emission tomography (PET) scans to measure amyloid (one of the protein pathological markers of AD) from participants in an ongoing community-based study of aging and dementia (WHICAP). The study will include subjects who are already enrolled in the parent project. Further, this study will enroll both subjects who have never been evaluated with PET scans and those who received a previous baseline PET scan. The study plans to obtain approximately 30 repeat amyloid PET scans and 20 baseline PET scans. The investigators will also conduct transcranial Doppler studies to measure blood flow in the participants with amyloid PET scans. The potential benefits to society should be considerable if this study reveals new information about risk factors for or contributions to AD.
Detailed description
Alzheimer's disease (AD) is one of the most devastating international public health epidemics. There are currently no effective disease-modifying or preventative strategies. Current pathogenic models emphasize a single pathway of disease pathogenesis, but underestimate the contribution of small vessel cerebrovascular disease, which manifests primarily as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). Understanding of the factors that drive the relationship between vascular disease and AD remains elusive; vascular factors may be independent sources of dysfunction that contribute additively to clinical expression, they may interact mechanistically with AD pathology, and/or they may relate to each other because of a shared association with a third set of factors. These issues are particularly relevant among ethnic/racial minorities, who are at much greater risk for clinical AD, have more severe cerebrovascular disease, but appear to have similar levels of AD pathology compared with Whites.
The proposed research examines these factors in a large, longitudinal, multi-ethnic community-based cohort study of older adults in northern Manhattan, New York. The investigators demonstrated that accumulation of WMH, particularly in parietal lobes, predicts incident AD, and is associated with the presence of cerebral microbleeds, an indicator of cerebral amyloid angiopathy. The investigators extend the research to examine mechanistic interactions between cerebrovascular disease and AD. The preliminary data suggest that individuals with evidence of fibrillar amyloidosis have increased parietal lobe WMH and that hemodynamic markers of autoregulatory dysfunction are associated with both WMH and amyloid deposition, which in turn interact to promote the clinical expression of AD. These findings are buffered by new data that establish WMH as a core feature in autosomal dominant forms of AD. In this pilot study, the investigators propose to obtain cross-sectional and longitudinal MRI and amyloid PET data from participants in WHICAP.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Radiation: Florbetaben F18, Procedure: Transcranial DopplerAll participants will undergo an amyloid PET scan with Florbetaben F 18 contrast as well as a transcranial Doppler ultrasound. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Potential participants are recruited from a list of active members in the Washington Heights/Hamilton Heights/ Inwood Columbia Aging Project, known as WHICAP (CU IRB# AAAO9804), who previously completed a repeat MRI as part of a neuroimaging sub-study (IRB# AAAO9758). Some participants (n=30) will already have had baseline amyloid PET imaging under PI IRB protocol # 7130R (BAY 949172PET/CT in Older Adults).
Key inclusion criteria (3 listed)
- current participant in WHICAP (Washington Heights/Inwood Columbia Aging Project)
- subject previously participated in baseline MRI sub-study
- post-menopausal
Key exclusion criteria (6 listed)
- allergic to Florbetaben
- claustrophobic
- liver problems
- history of epilepsy/seizures
- pre-menopausal
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 |
|---|---|---|
| Florbetaben F1810Meq of Florbetaben F 18 via intravenous injection is to be used. Visit duration is approximately 3 hours. | Radiation | Group A |
| Transcranial DopplerAll participants will undergo Doppler ultrasonography that measures the velocity of blood flow through the brain's blood vessels. Visit duration is approximately 45 minutes and will be scheduled for either the same day or another day as the PET scan. | Procedure or surgery | Group A |
Primary outcome
PET amyloid Standard Uptake Value ratio (SUVr) values
Time frame: up to 18 months
The primary outcome is the mean standard uptake value ratio in the 4 regions of interest.
Transcranial Doppler (TCD) dynamic autoregulatory dysfunction
Time frame: up to 18 months
Cerebral blood flow velocities (CBFV) are assessed using TCD. Arterial blood pressure (ABP) is recorded simultaneously using the Finapres on the middle phalanx of the left or right middle finger. The phase shift between the two streaming signals is an indication of the extent to which oscillations in CBFV lead those in ABP and can be interpreted as active early counter-regulation. Lower phase shift reflects increased latency in cerebral vasomotion and thus poorer autoregulation.
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 12 Sep 2019.
- Individual participant dataSharing planned: No
Related trials for Alzheimer Disease
Recruiting
Automated Language Analysis in Neurodegenerative Diseases: Application of Artificial Intelligence Models
Alzheimer's Disease (AD), Frontotemporal Dementia (FTD)
Enrolling by invitationPhase 2
Tau PET Outcomes With Anti-amyloid Immunotherapies
Cognitive Impairment, Mild, Dementia, Mild
Active, not recruiting
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Trial
Dementia, Cognitive Impairment
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
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.
Adam M Brickman, PhD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease and White Matter Hyperintensities, run by Columbia University 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 3 inclusion and 6 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 12 Sep 2019. 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.
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?
PET amyloid Standard Uptake Value ratio (SUVr) values (time frame: up to 18 months). 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?
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 12 Sep 2019.