PET Measures of CSF Clearance in Preclinical Alzheimer's Disease

NCT03663387 | Completed

• 2 other identifiers: 18040191811RF1AG057570-01
• Study Type: observational
• Target: 116
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• Percent change in brain amyloid

  Percent change in brain amyloid measured by positron emission tomography

  Baseline and 24 Months follow-up

• Percent change in cortical ribbon thickness

  Percent change in cortical ribbon thickness measured by magnetic resonance imaging

  Baseline and 24 Months follow-up

Study Arms (1)

Normal subjects

70

Eligibility Criteria

• Age: 20 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Biospecimen

Blood incl. geneting testing/APE Genotyping, CSF

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Mony J de Leon, ED.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: September 10, 2018
• Study Start: July 30, 2018
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: October 20, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made available through the Brain Health Imaging Institute at Weill Cornell Medicine through correspondence with mdl4001@med.cornell.edu
• Access Criteria: Anyone who wishes to access the data who will provide a methodologically sound proposal.

Locations

US (1)