Mild Cognitive ImpairmentNCT03663387
PET Measures of CSF Clearance in Preclinical Alzheimer's Disease
An observational study of Mild Cognitive Impairment, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
The purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Read more about this study
- Who is it for?
- Ages 20 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- How many people
- 116 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2018to 31 Aug 2022
- 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 20 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This study will involve male and female volunteer subjects from any racial or ethnic group with a diagnosis normal cognition or mild cognitive impairment. The proposed sample is not intended to be representative of a general population, but it will approximate the samples recruited in NIH and industry sponsored FDA approved clinical trials targeting secondary AD prevention. At this stage of knowledge of human brain CSF clearance, a population based approach was considered premature and over cap funding to support a larger study was not permitted for RFA AG-17-055. Rather, our design uses Aβ enrichment to enable an efficient test of the CSF clearance hypothesis in a clinically relevant group.
Who may be able to join
- Male and female subjects between 20-100 years old will be enrolled. Younger subjects are not included as the risk for brain amyloid lesions is too low
- All subjects will speak English as their first language or demonstrate proficiency in English.
- All subjects may have normal cognition or cognitive impairment.
- All subjects will be in good general health and able to participate in the LP and imaging exams. This determination is made by the study neurologist and reviewed at a consensus meeting for each subject.
Who cannot join
- Uncontrolled hypertension or metabolic disease
- Neurodegenerative disorders (i.e. Parkinson disease. LBD, or FTD).
- Long life major depression. Baseline scores ≥20 on Beck Depression Inventory at baseline
- Long-life DSM-IV axis 1 disorders.
- Mental retardation.
- Substance abuse.
Show all 24Show fewer
- Concurrent medication limiting validity of neuropsychological tests or imaging.
- Anti-depressants with anti-cholinergic properties
- Monoamine oxidase inhibitors (MAOi)
- Regular use of narcotic analgesics (>2 doses per week).
- Use of neuroleptics
- Individuals taking over the counter memory enhancing or protecting medications (e.g. ginkgo biloba, vitamins) are not excluded.
- Implanted medical devices that are incompatible with MRI imaging.
- Radiation exposures exceeding annual Rad Worker limits.
- Heart failure stage D as defined by American Heart Association (7).
- Chronic kidney disease in stages ≥ 4, as defined per National Kidney Foundation (8).
- Brain tumor and other neoplastic disorders outside the brain where disease itself or its treatment (radiation, chemotherapy) is likely to affect brain structure or function.
- Stroke when meeting criteria for total anterior, partial anterior or posterior circulation infarct according to the Oxford Community Stroke Project classification. Patients with clinically silent of lacunar strokes and transient ischemic attacks will not be excluded.
- Significant head trauma.
- Hydrocephalus.
- Hostility or refusal to cooperate
- Person's receiving chronic anti-coagulation therapy
- Person's participating in other research projects will be excluded when the other project(s) 1) involve radiation exposure which in combination with the current project would increase radiation exposure above federal guidelines, 2) involve administration of study drug or other experimental therapy, or 3) prohibit participation in other research projects.
- Participants in this study will be allowed to participate in other observational research studies. The investigators will review at enrollment the full array of projects a subject may be involved in and inform the other PI's to ensure that subject safety and research data integrity is not compromised.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Researchers have considered that impaired clearance of amyloid (a protein) from the aging brain causes buildup of amyloid in the brain and plays a role in increased risk for Alzheimer's disease. However, until recently, there has not been a method to measure CSF clearance. This study will examine CSF clearance using positron emission tomography (PET) scanning, which creates images of structures in the body and their functioning. This study will also measure the amount of two proteins, tau and amyloid, in the brain. Tau and amyloid are proteins that build up in the brains of people with Alzheimer's disease. An investigational compound (tracer) called [18F]MK-6240 is injected into the blood prior to the scan in order to take images of the CSF clearance and measure tau protein in the brain. This tracer is considered investigational because it is not approved by the US Food and Drug Administration (FDA) for clinical use and is only being used for research purposes.
Read the detailed description
The impaired clearance of amyloid-β (Aβ) leading to the accumulation of Aβ plaques and consequent neurodegeneration, is a partially understood mechanistic hypothesis for late onset Alzheimer's disease (AD). Using Positron Emission Tomography (PET) and a tracer for tau lesions, with a low molecular weight that rapidly enters and clears the brain, the investigators developed, replicated, and validated a non-invasive method to estimate the clearance of CSF at ventricular and brain levels. The investigators propose to complete over five years, a 2y longitudinal study designed to test in preclinical AD the hypothesis that reduced CSF clearance measured with the tau tracer [18F]-MK6240 is predictive of: a) future amyloid lesions (PiB-PET or Florbetaben-PET); b) brain atrophy (MRI); and c) cognitive decline.
- Conditions
- Mild Cognitive Impairment
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Normal subjects | 70 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in brain amyloid
Percent change in brain amyloid measured by positron emission tomography
Measured: Baseline and 24 Months follow-up
Percent change in cortical ribbon thickness
Percent change in cortical ribbon thickness measured by magnetic resonance imaging
Measured: Baseline and 24 Months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start30 Jul 2018
- Primary completion31 Aug 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell 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
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Mony J de Leon, ED.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03663387
- Sponsor's protocol ID
- 1804019181
- Other IDs
- 1RF1AG057570-01
- Status last verified
- Oct 2022
- First submitted
- 10 Aug 2018
- Last updated
- 20 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Measures of CSF Clearance in Preclinical Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03663387
- Acronym / sponsor ID
- 1804019181
- Conditions
- Mild Cognitive Impairment
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 30 Jul 2018 (actual)
- Primary completion
- 31 Aug 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 10 Sep 2018 (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 purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Researchers have considered that impaired clearance of amyloid (a protein) from the aging brain causes buildup of amyloid in the brain and plays a role in increased risk for Alzheimer's disease. However, until recently, there has not been a method to measure CSF clearance. This study will examine CSF clearance using positron emission tomography (PET) scanning, which creates images of structures in the body and their functioning. This study will also measure the amount of two proteins, tau and amyloid, in the brain. Tau and amyloid are proteins that build up in the brains of people with Alzheimer's disease. An investigational compound (tracer) called [18F]MK-6240 is injected into the blood prior to the scan in order to take images of the CSF clearance and measure tau protein in the brain. This tracer is considered investigational because it is not approved by the US Food and Drug Administration (FDA) for clinical use and is only being used for research purposes.
Detailed description
The impaired clearance of amyloid-β (Aβ) leading to the accumulation of Aβ plaques and consequent neurodegeneration, is a partially understood mechanistic hypothesis for late onset Alzheimer's disease (AD). Using Positron Emission Tomography (PET) and a tracer for tau lesions, with a low molecular weight that rapidly enters and clears the brain, the investigators developed, replicated, and validated a non-invasive method to estimate the clearance of CSF at ventricular and brain levels. The investigators propose to complete over five years, a 2y longitudinal study designed to test in preclinical AD the hypothesis that reduced CSF clearance measured with the tau tracer [18F]-MK6240 is predictive of: a) future amyloid lesions (PiB-PET or Florbetaben-PET); b) brain atrophy (MRI); and c) cognitive decline.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Normal subjects | – | –70 |
Who may qualify
- Ages
- 20 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This study will involve male and female volunteer subjects from any racial or ethnic group with a diagnosis normal cognition or mild cognitive impairment. The proposed sample is not intended to be representative of a general population, but it will approximate the samples recruited in NIH and industry sponsored FDA approved clinical trials targeting secondary AD prevention. At this stage of knowledge of human brain CSF clearance, a population based approach was considered premature and over cap funding to support a larger study was not permitted for RFA AG-17-055. Rather, our design uses Aβ enrichment to enable an efficient test of the CSF clearance hypothesis in a clinically relevant group.
Key inclusion criteria (4 listed)
- Male and female subjects between 20-100 years old will be enrolled. Younger subjects are not included as the risk for brain amyloid lesions is too low
- All subjects will speak English as their first language or demonstrate proficiency in English.
- All subjects may have normal cognition or cognitive impairment.
- All subjects will be in good general health and able to participate in the LP and imaging exams. This determination is made by the study neurologist and reviewed at a consensus meeting for each subject.
Key exclusion criteria (24 listed)
- Uncontrolled hypertension or metabolic disease
- Neurodegenerative disorders (i.e. Parkinson disease. LBD, or FTD).
- Long life major depression. Baseline scores ≥20 on Beck Depression Inventory at baseline
- Long-life DSM-IV axis 1 disorders.
- Mental retardation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percent change in brain amyloid
Time frame: Baseline and 24 Months follow-up
Percent change in brain amyloid measured by positron emission tomography
Percent change in cortical ribbon thickness
Time frame: Baseline and 24 Months follow-up
Percent change in cortical ribbon thickness measured by magnetic resonance imaging
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 20 Oct 2022.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
Related trials for Mild 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
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
RecruitingObservational study
InRAD Observational Study
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Recruiting
Treating Insomnia in Mild Cognitive Impairment
Mild Cognitive Impairment (MCI), Insomnia
Recruiting
Telehealth-Adapted Compensatory Training and Intervention for Cognition
MCI, Mild Cognitive Impairment
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.
Mony J de Leon, ED.D. principal investigator
Weill Medical College of Cornell 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 Mild Cognitive Impairment, run by Weill Medical College of Cornell 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 4 inclusion and 24 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 20 Oct 2022. 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?
Percent change in brain amyloid (time frame: Baseline and 24 Months follow-up). 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 20 Oct 2022.