Alzheimer DiseaseNCT04510168
Accelerated Non-Atherosclerotic Brain Arterial Aging Relationship to Alzheimer's Disease
An observational study of Alzheimer Disease and Dementia, run by Jose Gutierrez, MD, MPH at 1 site in United States.
Trial summary
The aging of the United States (US) population will lead to a steep rise in Alzheimer disease (AD). There is an urgent need for novel therapies that may tackle this looming societal problem. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Dementia
- What is being tested?
- 11C-ER176, [F-18]MK-6240 and Florbetaben
- How many people
- 238 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Sep 2020to 17 Apr 2024
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The population targeted in this aim comes from the long-established NOMAS study, an ongoing, prospective, population-based cohort of 3,298 stroke-free participants. Cohort recruitment occurred from 1993 to 2001. Initial eligibility for the cohort included those aged > 40 years who were permanent residents of Northern Manhattan, lived in a house with a telephone, and had no history of clinical stroke. NOMAS participants were recruited during annual follow-ups to undergo a brain MRI if they met the following criteria: free of clinical stroke, aged >50 years, and could have an MRI.
Who may be able to join
- Age 50 and older
- Being part of the NOMAS MRI substudy
- Subjects unable to provide informed consent must have a surrogate decision maker
- Written and oral fluency in English or Spanish
- Able to participate in all scheduled evaluations and to complete all required tests and procedures.
- In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.
Who cannot join
- Past or present history of certain brain disorders other than Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) (self-reported brain tumor, dementia of Lewy body, frontotemporal dementia).
- Certain significant medical conditions, which make study procedures of the current study unsafe (liver cirrhosis, end-stage renal disease on dialysis, terminal cancer (death expected within 6 months)).
- Contraindication to MRI scanning
- Conditions precluding entry into the scanners (e.g., morbid obesity, claustrophobia, etc.).
- Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
- Participation in a clinical trial for a disease-modifying drug for AD the year prior to the date of the first PET scan.
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- Inability to have a catheter in subject's vein for the injection of radioligand.
- Inability to have blood drawn from subject's veins.
- Subjects will not be included in the study if they have participated in the last year in a clinical trial for a disease-modifying drug for AD.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
The aging of the United States (US) population will lead to a steep rise in Alzheimer disease (AD). There is an urgent need for novel therapies that may tackle this looming societal problem. People with Alzheimer disease have frequently evidence of vascular disease in the brain, and vascular disease can increase the risk of Alzheimer disease. Based on this finding, the investigators plan to expand the understanding of how vascular disease contributes to Alzheimer disease, hoping to identify novel target to modify the natural progression of the disease. The investigators will accomplish this goal by inviting 300 participants (with and without dementia) of the Northern Manhattan Study (NOMAS) to undergo a brain magnetic resonance imaging (MRI) and donate blood. Of the 300 participants enrolled, 60 participants will be randomly selected to undergo Aβ and tau positron emission tomography (PET) imaging.
From the brain MRI, the investigators will obtain measurements of cerebrovascular disease and relate the to the risk of Alzheimer disease. With the blood, the investigators hope to identify measures of aging and inflammation that may predict changes noted in brain scan and identify people at a higher risk of dementia. The investigators will examine PET markers of inflammation and aging in the brain and how the markers relate to dementia.
Read the detailed description
Research about non-atherosclerotic BAA and its effects on cognition has been hampered by the lack of high-resolution arterial wall imaging, the preponderance of research focused on intracranial large artery atherosclerosis (ILAA) and the lack of mechanistic studies. This study aims to address these shortcomings. By using high-resolution brain arterial wall imaging in participants in the NOMAS cohort, the investigators will derive a wall-based measure of non-atherosclerotic BAA and relate it to pre-MRI cognitive trajectories, AD risk, and ipsilateral markers of neurodegeneration including Aβ/tau PET imaging.
- Conditions
- Alzheimer Disease, Dementia
- Being tested
- 11C-ER176, [F-18]MK-6240, Florbetaben, Magnetic Resonance Imaging
- Keywords
- Vascular Disease, Non-Atherosclerotic Brain Arterial Aging
- Medical subject headings
- Alzheimer Disease, Dementia, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-ER176Drug
PET imaging to measure 18kDa translocator protein; target imaging dose of up to 20 millicurie (mCi)
[F-18]MK-6240Drug
PET imaging to measure tau; target imaging dose of 4 to 5 mCi
FlorbetabenDrug
Also called NeuraCeq
PET radioligand that binds to amyloid plaques; target-imaging dose of up to 8.1 mCi
Magnetic Resonance ImagingOther
Brain MRI
| Study group | Role | What they receive |
|---|---|---|
| MRI Only | The investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project (NOMAS) participants. The investigators aim to include at least 50-60 people with dementia (as determined by the ongoing NOMAS procedures). Receives: Other: Magnetic Resonance Imaging | |
| MRI and PET | The investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study (NOMAS) participants. The investigators aim to include at 20 participants with dementia and 40 participants without (as determined by the ongoing NOMAS procedures). In addition to MRI, participants in this group will have three PET studies. Receives: Drug: 11C-ER176; Drug: [F-18]MK-6240; Drug: Florbetaben; Other: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Standardized Uptake Values (SUVRs) of Florbetaben
Concentration of radioactivity of Florbetaben (to mark amyloid deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
Measured: Up to 1 month
Standardized Uptake Values (SUVRs) of 18F-MK- 6240
Concentration of radioactivity of 18F-MK- 6240 (to mark tau deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
Measured: Up to 1 month
Secondary outcomes (1)
Association Between Non-Atherosclerotic Brain Arterial Aging (BAA) and Prevalent Alzheimer's' Disease
Calculation of the effect size (estimated beta=0.024 +/- 0.0008) of the association between non-atherosclerotic brain arterial aging (BAA) and prevalent Alzheimer's' disease. Each artery forming the circle of Willis and the vertebral arteries will be rated for measuring wall thickness, lumen diameter, lumen-to-wall ratio, and pattern of thickness. The investigators will use spline regression plots to inform the best cutoff to define "thickened arterial wall" and "dilated artery" (based on time of flight MRA). The BAA score will be the sum of three variables: presence of thickened wall, dilated artery, and concentric wall thickening.
Measured: Up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2020
- Study start18 Sep 2020
- Primary completion16 Apr 2024
- Study completion17 Apr 2024
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.
- 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
- 238 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jose Gutierrez, MD, MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jose Gutierrez, MD, MPH, Columbia University
- Investigators
- Jose Gutierrez, MD, MPH, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04510168
- Sponsor's protocol ID
- AAAS7441
- Other IDs
- R01 AG06616201
- Status last verified
- Jul 2024
- First submitted
- 10 Aug 2020
- Last updated
- 16 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated Non-Atherosclerotic Brain Arterial Aging Relationship to Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04510168
- Acronym / sponsor ID
- AAAS7441
- Conditions
- Alzheimer Disease, Dementia
- Keywords
- Vascular Disease, Non-Atherosclerotic Brain Arterial Aging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 238 participants (actual)
- Lead sponsor
- Jose Gutierrez, MD, MPHUniversity, hospital or other
- Study start
- 18 Sep 2020 (actual)
- Primary completion
- 16 Apr 2024 (actual)
- Study completion
- 17 Apr 2024 (actual)
- First posted
- 12 Aug 2020 (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.
The aging of the United States (US) population will lead to a steep rise in Alzheimer disease (AD). There is an urgent need for novel therapies that may tackle this looming societal problem. People with Alzheimer disease have frequently evidence of vascular disease in the brain, and vascular disease can increase the risk of Alzheimer disease. Based on this finding, the investigators plan to expand the understanding of how vascular disease contributes to Alzheimer disease, hoping to identify novel target to modify the natural progression of the disease. The investigators will accomplish this goal by inviting 300 participants (with and without dementia) of the Northern Manhattan Study (NOMAS) to undergo a brain magnetic resonance imaging (MRI) and donate blood. Of the 300 participants enrolled, 60 participants will be randomly selected to undergo Aβ and tau positron emission tomography (PET) imaging.
From the brain MRI, the investigators will obtain measurements of cerebrovascular disease and relate the to the risk of Alzheimer disease. With the blood, the investigators hope to identify measures of aging and inflammation that may predict changes noted in brain scan and identify people at a higher risk of dementia. The investigators will examine PET markers of inflammation and aging in the brain and how the markers relate to dementia.
Detailed description
Research about non-atherosclerotic BAA and its effects on cognition has been hampered by the lack of high-resolution arterial wall imaging, the preponderance of research focused on intracranial large artery atherosclerosis (ILAA) and the lack of mechanistic studies. This study aims to address these shortcomings. By using high-resolution brain arterial wall imaging in participants in the NOMAS cohort, the investigators will derive a wall-based measure of non-atherosclerotic BAA and relate it to pre-MRI cognitive trajectories, AD risk, and ipsilateral markers of neurodegeneration including Aβ/tau PET imaging.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MRI Only | – | Other: Magnetic Resonance ImagingThe investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project (NOMAS) participants. The investigators aim to include at least 50-60 people with dementia (as determined by the ongoing NOMAS procedures). |
| MRI and PET | – | Drug: 11C-ER176, Drug: [F-18]MK-6240, Drug: Florbetaben, Other: Magnetic Resonance ImagingThe investigators will acquire de-novo brain MRI and time-of-flight MRA in randomly selected surviving Northern Manhattan Study (NOMAS) participants. The investigators aim to include at 20 participants with dementia and 40 participants without (as determined by the ongoing NOMAS procedures). In addition to MRI, participants in this group will have three PET studies. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The population targeted in this aim comes from the long-established NOMAS study, an ongoing, prospective, population-based cohort of 3,298 stroke-free participants. Cohort recruitment occurred from 1993 to 2001. Initial eligibility for the cohort included those aged > 40 years who were permanent residents of Northern Manhattan, lived in a house with a telephone, and had no history of clinical stroke. NOMAS participants were recruited during annual follow-ups to undergo a brain MRI if they met the following criteria: free of clinical stroke, aged >50 years, and could have an MRI.
Key inclusion criteria (6 listed)
- Age 50 and older
- Being part of the NOMAS MRI substudy
- Subjects unable to provide informed consent must have a surrogate decision maker
- Written and oral fluency in English or Spanish
- Able to participate in all scheduled evaluations and to complete all required tests and procedures.
Key exclusion criteria (9 listed)
- Past or present history of certain brain disorders other than Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) (self-reported brain tumor, dementia of Lewy body, frontotemporal dementia).
- Certain significant medical conditions, which make study procedures of the current study unsafe (liver cirrhosis, end-stage renal disease on dialysis, terminal cancer (death expected within 6 months)).
- Contraindication to MRI scanning
- Conditions precluding entry into the scanners (e.g., morbid obesity, claustrophobia, etc.).
- Exposure to research related radiation in the past year that, when combined with this study, would place subjects above the allowable limits.
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-ER176PET imaging to measure 18kDa translocator protein; target imaging dose of up to 20 millicurie (mCi) | Drug | MRI and PET |
| [F-18]MK-6240PET imaging to measure tau; target imaging dose of 4 to 5 mCi | Drug | MRI and PET |
| FlorbetabenAlso: NeuraCeqPET radioligand that binds to amyloid plaques; target-imaging dose of up to 8.1 mCi | Drug | MRI and PET |
| Magnetic Resonance ImagingBrain MRI | Other | MRI Only, MRI and PET |
Primary outcome
Standardized Uptake Values (SUVRs) of Florbetaben
Time frame: Up to 1 month
Concentration of radioactivity of Florbetaben (to mark amyloid deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
Standardized Uptake Values (SUVRs) of 18F-MK- 6240
Time frame: Up to 1 month
Concentration of radioactivity of 18F-MK- 6240 (to mark tau deposition) in each target region of interest (prefrontal cortex, superior temporal gyrus, combined middle/inferior temporal gyri, medial temporal cortex, superior parietal lobule, inferior parietal lobule, posterior cingulate cortex, and occipital cortex) will be divided by that in cerebellar gray matter to calculate standardized uptake values (SUVRs).
1 secondary outcome
Association Between Non-Atherosclerotic Brain Arterial Aging (BAA) and Prevalent Alzheimer's' Disease
Time frame: Up to 1 month
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 16 Jul 2024.
- Individual participant dataSharing planned: Undecided
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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.
Jose Gutierrez, MD, MPH 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 Dementia, run by Jose Gutierrez, MD, MPH 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 9 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 16 Jul 2024. 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?
Standardized Uptake Values (SUVRs) of Florbetaben (time frame: Up to 1 month). 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 16 Jul 2024.