Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers. (Protocol Z)

• ClinicalTrials.gov Identifier: NCT03816228
• Recruitment Status: Recruiting
• First Posted: January 25, 2019
• Last Update Posted: October 14, 2021
• Sponsor: Tammie L. S. Benzinger, MD, PhD
• Information provided by (Responsible Party): Tammie L. S. Benzinger, MD, PhD, Washington University School of Medicine

Study Description

Brief Summary:

This is a multi-center study at Washington University (WASH U), University of Southern California (USC), and Huntington Medical Research Institute (HMRI).The overall goal of both the AA program and the PPG program is to advance current knowledge on the vascular contributions to dementia particularly in individuals with the major genetic risk factor for late-onset AD, i.e., apolipoprotein E-ε4 (APOE4) gene that develop early vascular dysfunction and significant cerebrovascular pathology compared to non-carriers, and establish whether the neurovasculature plays a key role in cognitive decline, and therefore is a key new therapeutic target to treat dementia in APOE4 carriers.

Condition or disease	Intervention/treatment
Alzheimer Disease	Drug: F 18 T807 Flortaucipir

Study Design

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers. (IND 123119, Protocol Z)
• Estimated Study Start Date: November 15, 2021
• Estimated Primary Completion Date: January 2025
• Estimated Study Completion Date: June 2025

Groups and Cohorts

Group/Cohort	Intervention/treatment
Experimental Flortaucipir	Drug: F 18 T807 Flortaucipir; 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 Name: 18F-AV-1451

Outcome Measures

Primary Outcome Measures :

1. F 18 T807 Standard Uptake Value Ratios [ Time Frame: 5 years ]
   F 18 T807 Standard Uptake Value Ratios (SUVR) will be correlated with other imaging modalities (MRI, PET amyloid imaging) and cognitive performance.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

A total of participants currently enrolled in ongoing projects affiliated with the Knight ADRC will be recruited. Without disclosing individual genetic risk status, 202 of these participants will include a mix of APOE4/4 (~7%), APOE3/4 (~30%), and APOE3/3 (~63%) carriers. In addition, without disclosing individual mutation status, ~40 PSEN1 carriers and non-carrier family members currently enrolled in the Dominantly Inherited Alzheimer Network (DIAN) study at Washington University will be recruited.

Criteria

Inclusion Criteria:

• Male or female, any race
• Age > 18 years
• Participation in one of the ongoing projects affiliated with the Knight ADRC at Washington University and referred by the MAP staff and a Washington University physician.
• Normal cognition or early-stage symptomatic AD
• Females of childbearing potential without documented history of menopause or hysterectomy who do participate must not be pregnant or breastfeeding at screening
• (negative urine β-HCG within 24 hours prior to injection), and must agree to avoid becoming pregnant. Females of childbearing potential who do not agree to use reliable contraception or refrain from sexual activity for 24 hours following administration of flortaucipir injection.
• Enrollment in DCE-MRI study
• Capacity to give informed consent and follow study procedures

Exclusion Criteria:

• Any illness preventing cooperation with testing or longitudinal participation
• Exclusion from the Knight ADRC or DIAN referring project
• Has a high risk for Torsades de Pointes or is taking medications known to prolong or may prolong QT interval (refer to study attachment "Restricted Medication List").
• MRI contraindications (e.g. electronic medical devices, severe claustrophobia, inability to lie still for long periods) that make it unsafe to participate in an MRI scan, using standard screening processes implemented by Washington University and Barnes-Jewish Hospital
• Currently pregnant or breastfeeding

Contacts and Locations

Contacts

Contact: Kelley Jackson, BA; 314-362-1558; jacksonk@wustl.edu

Locations

United States, Missouri

Washington University School of Medicine; Recruiting

Saint Louis, Missouri, United States, 63110

Contact: LaKisha Lloyd, MS 314-319-7874 lloydl@wustl.edu

Sponsors and Collaborators

Tammie L. S. Benzinger, MD, PhD

Investigators

• Principal Investigator: Tammie Benzinger, MD, PhD; Washington University School of Medicine

More Information

Publications:

Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN. Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer's disease and vascular dementia. Curr Alzheimer Res. 2013 Jul;10(6):642-53. Review.

Fleisher A, Grundman M, Jack CR Jr, Petersen RC, Taylor C, Kim HT, Schiller DH, Bagwell V, Sencakova D, Weiner MF, DeCarli C, DeKosky ST, van Dyck CH, Thal LJ; Alzheimer's Disease Cooperative Study. Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Arch Neurol. 2005 Jun;62(6):953-7.

Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985-92. Review.

• Responsible Party: Tammie L. S. Benzinger, MD, PhD, Professor of Radiology & Neurological Surgery, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03816228
• Other Study ID Numbers: IND 123119 Protocol Z
• First Posted: January 25, 2019
• Last Update Posted: October 14, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: We will share the data with other researchers. They 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. We may also share the research data with large data repositories (a repository is a database of information) for broad sharing with the research community. The participant"s individual research data is placed in one of these repositories only qualified researchers, who have received prior approval from individuals that monitor the use of the data, will be able to look at this information.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tammie L. S. Benzinger, MD, PhD, Washington University School of Medicine:

Dementia; Taupathies; Brain Disease; Mild Cognitive Impairment; Neurodegenerative Disease

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders