PET Measures of CSF Clearance in Preclinical Alzheimer's Disease

October 18, 2022 updated by: Weill Medical College of Cornell University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
116

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Normal subjects
70

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent change in brain amyloid
Time Frame: Baseline and 24 Months follow-up
Percent change in brain amyloid measured by positron emission tomography
Baseline and 24 Months follow-up
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
Baseline and 24 Months follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weill Medical College of Cornell University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mony J de Leon, ED.D., Weill Medical College of Cornell University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 30, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 10, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 20, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 18, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1804019181
  • 1RF1AG057570-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All of the individual participant data collected during the trial, after deidentification.

IPD Sharing Time Frame

Data will be made available through the Brain Health Imaging Institute at Weill Cornell Medicine through correspondence with mdl4001@med.cornell.edu

IPD Sharing Access Criteria

Anyone who wishes to access the data who will provide a methodologically sound proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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