Evaluating the Relationship Between Tau PET Imaging and CSF Biomarkers of AD (Alzheimer Disease) in Humans (ADRCproj1)

Evaluating the Relationship Between Tau PET Imaging and CSF Biomarkers of AD in Humans

The purpose of this research study is to evaluate a new radioactive compound used in positron emission tomography (PET) scans in identifying tau tangles (a certain protein that might be associated with Alzheimer's disease) in the brain, and if the amount of tau tangles in the brain has a relationship to cerebrospinal fluid (CSF) biomarkers and cognitive status.

This study involves a PET scans using the radioactive compound, F 18 T807 for measurement of tau deposition. This radioactive compound is not approved by the United States Food and Drug Administration (FDA). An MRI will be conducted if one has not been completed completed within the past 12 months under a related research study. Participants will be asked about their medical history, family history, surgical history, and current medications. We will evaluate history of traumatic brain injury (TBI) using the Ohio State University Traumatic Brain Injury Identification (OSU TBI-ID) Method. This will take approximately 10 minutes. Participants will be asked to undergo a Mini Mental State Examination (MMSE), which will last approximately 5-10 minutes.

Additionally, participants may be invited to undergo optional brain PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose fludeoxyglucose (18F-FDG), for measurement of the cerebral metabolic rate of glucose consumption. At the time of the initial T807-PET study, participants will be asked if they are willing to undergo repeat T807-PET imaging at least 2 years after the initial study. This follow up study is optional, and participation in the study and initial T807-PET imaging will not be contingent on agreeing to the 2-year follow up study.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: 18F-AV-1451

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Under this study protocol, collaborating physicians and the Knight Alzheimer's Disease Research Center (ADRC) Clinical Core will refer participants to the Knight ADRC Research Imaging (KARI) Program for MR and PET imaging to evaluate tau distribution in the brains of cognitively normal and cognitively impaired individuals.

Description

Inclusion Criteria:

1. Male or female participants, at least 65 years of age.
2. Participant is willing to undergo a lumbar puncture (LP) or has previously undergone LP. LP will be conducted under IRB ID 201109100 (PI: Anne Fagan).
3. Participant is able and willing to undergo positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain.
4. Pre-menopausal women must have a negative urine pregnancy test within 24 hours preceding T807 drug administration.

Exclusion Criteria:

1. Has any condition that, in the Investigator's opinion, could increase risk to the participant, limit the participant's ability to tolerate the experimental procedures, or interfere with the collection/analysis of the data (for example, participants with severe chronic back pain might not be able to lie still during the scanning procedures).
2. Is deemed likely unable to perform the imaging procedures for any reason.
3. Has a history of Torsades de Pointes or is taking medications known to prolong or may prolong QT interval (refer to study's list of restricted medications).
4. Has known hypersensitivity to T807 or any of its excipients.
5. Contraindications to PET, PET-CT or MR (e.g. electronic medical devices, inability to lie still for long periods) that make it unsafe for the individual to participate.
6. Severe claustrophobia.
7. Currently pregnant or breast-feeding. -

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental 18F-AV-1451	Drug: 18F-AV-1451; Participants will receive a single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807. For those who cannot tolerate the full exam, participants will receive single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807.; Other Names: Flortauapir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Examine the association among T807-PET measures of PHF-tau.	5 years
Characterize the amount and spatial distribution of T807-PET measures in healthy aging. preclinical AD, and early symptomatic AD.	5 years
Characterize the amount and spatial distribution of T807-PET measures in preclinical AD.	5 years
Characterize the amount and spatial distribution of T807-PET measures in early symptomatic AD.	5 years
Examine the association among T807-PET measures of concentrations of CSF biomarkers. and cognitive performance.	5 years
Examine the association among T807-PET measures of cognitive performance.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate the change in T807-PET measures over time in asymptomatic amyloid-positive individuals and its association with changes in concentrations of CSF biomarkers.	5 years

Collaborators and Investigators

• Sponsor: Tammie L. S. Benzinger, MD, PhD
• Investigators: Principal Investigator: Tammie Benzinger, MD, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): July 19, 2021

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Dementia; cognitive impairment; Tauopathies; neurodegenerative disease; CNS Diseases
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: IND123119,Protocol F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Investigators may share the participant's data with other researchers that may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at Washington University, at other research centers and institutions, or industry sponsors of research. The Investigators may also share the research data with large data repositories (a repository is a database of information) for broad sharing with the research community. If the individual research data is placed in one of these repositories only qualified researchers will be able to look at the information.