Clinical trial NCT03816228: Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers.
Official title: Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers. (IND 123119, Protocol Z)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Alzheimer Disease
Keywords: Dementia
Taupathies
Brain Disease
Mild Cognitive Impairment
Neurodegenerative Disease
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2019-01-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

Brief summary: To advance current knowledge on the vascular contributions to dementia

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: F 18 T807 Standard Uptake Value Ratios
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Tammie Benzinger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.2174/15672050113109990037.
citation: 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. doi: 10.1001/archneur.62.6.953.
citation: 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. doi: 10.1001/archneur.58.12.1985.