PET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using PI-2620

Alzheimer Disease Clinical Trial

Official title: Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Disease Using the PET Ligand PI-2620

Status Recruiting

Clinical Trial Summary

The investigators will compare PI-2620 tau PET scans from patients with frontotemporal lobar degeneration (FTLD), patients with non-amnestic presentations of Alzheimer's disease (naAD), and demographically matched cognitively normal seniors.

Clinical Trial Description

The current study is a companion imaging study to IRB# 842873, "University of Pennsylvania Centralized Observational Research Repository on Neurodegenerative Disease" (UNICORN). UNICORN is an observational study that aims to collect and store cross-sectional and longitudinal data from brain imaging, clinical and neuropsychological assessment, biomarker assays, and genetic testing of participants to improve clinical assessment and basic scientific understanding of multiple neurodegenerative conditions. The UNICORN cohort includes neurodegenerative disease patients who have been evaluated by trained neurologists in the Penn Cognitive Neurology Clinic according to published clinical research diagnostic criteria and reviewed at a weekly multidisciplinary consensus conference; as well as individuals with normal cognition recruited from the general community or from among caregivers/relatives of patients participating in research. As part of the UNICORN study, participants are asked to undergo periodic (typically annual) magnetic resonance imaging (MRI) and clinical/neuropsychological assessment. Participants may also be asked to undergo genetic testing to detect known variants associated with increased neurodegenerative disease risk. UNICORN participants are also asked to undergo a one-time lumbar puncture to assess cerebrospinal fluid protein levels, including amyloid-ß1-42, an established biomarker for Alzheimer's disease (AD) neuropathologic change. As an alternative method of assessing amyloid status, some UNICORN participants may elect to undergo an [18F] florbetaben amyloid PET scan under protocol #824869.

All participants in the current study must be concurrently enrolled in UNICORN. The current study comprises a recruitment/screening visit and a single PET imaging scan using the PI-2620 tracer. The central hypotheses are 1) that PI-2620 PET will distinguish Alzheimer's disease (AD) or frontotemporal lobar degeneration (FTLD) tauopathy from the brains of both healthy seniors and patients with FTLD due to accumulation of transactive response DNA binding protein 43 kDA (TDP-43); and 2) that in FTLD and AD tauopathies, PI-2620 will be associated with patients' current and future cognitive, motor, and functional impairment.

Participants will be assigned to one of 7 groups, including cognitively and neurologically normal seniors (CN; planned enrollment of n=12); non-amnestic AD (naAD, n=15); frontotemporal lobar degeneration (FTLD) due to tauopathy (FTLD-tau, n=12); FTLD due to TDP-43 (n=12); FTLD-tau due to a known genetic mutation in the MAPT gene (genetic FTLD-tau, n=3); FTLD-TDP due to a known mutation in the GRN gene or open reading frame 72 of chromosome 9 (C9orf72) (genetic FTLD-TDP, n=3); and amnestic MCI/AD (aAD, n=15), Total planned enrollment is thus 72 participants; recruitment and data acquisition for the study are projected to take approximately 3 years. ;

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitively Normal
• Frontotemporal Lobar Degeneration

• NCT number: NCT05456503
• Study type: Interventional
• Source: University of Pennsylvania
• Contact: David J Irwin, MD
• Phone: 215-662-3361
• Email: dirwin@pennmedicine.upenn.edu
• Status: Recruiting
• Phase: Phase 3
• Start date: September 19, 2022
• Completion date: August 2026