Clinical trial NCT03545126: Human CNS Tau Kinetics in Tauopathies
Official title: Human CNS Tau Kinetics in Tauopathies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
Frontotemporal Dementia (FTD MAPT Mutation)
Keywords: Tauopathies
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Association of Frontotemporal Degeneration
name: Tau Consortium
First posted: 2018-06-04
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Progressive Supranuclear Palsy (PSP): N=12

Corticobasal Degeneration (CBD): N=8

Frontotemporal Dementia (FTD): MAPT: Family members with or at-risk of tau mutations (e.g. P301L) N=12

Brief summary: The goal of this study is to characterize tau kinetics and tau aggregation in the human CNS and to test the hypothesis that tau kinetics are altered (i.e. increased production, decreased clearance, and increased aggregation rate) in tauopathies.

Detailed description: Tauopathies are neurodegenerative diseases with tau pathology. These tauopathies are the most common pathology in neurodegenerative diseases, and they are reaching epidemic proportions. The rates of tau kinetics are central to understanding normal and abnormal processing and production and clearance of tau kinetics in humans to help understand the causes of tauopathy and evaluate tau-targeted therapeutics.

This study will utilize the Stable Isotope Labeling Kinetics (SILK) method to elucidate tau kinetics in vivo in the human central nervous system (CNS) and its alteration in tauopathies. A total of \~34 participants from 3 different neurodegenerative diseases: Frontotemporal Dementia (FTD), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP), will be invited to enroll in the study.

Participants will be labeled with stable isotopes via 16hr intravenous infusion and CSF samples collected during subsequent lumbar puncture visits over \~120 days. CSF will be analyzed over time for the quantitation of labeled tau.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with PSP, CBD, or FTD MAPT

Exclusion Criteria:

* Clotting disorder
* Active anticoagulation therapy
* Active infection
* Meningitis
* Recent syncope
* Current experimental treatment targeting Aβ or medications thought to influence Aβ production or clearance rates (benzodiazepines, muscarinic agents, or anti-epileptics)

Primary outcomes:
measure: Tau Fractional Turnover Rate (FTR)
timeFrame: 6 months
Secondary outcomes:
measure: CSF Tau Absolute Concentration
timeFrame: 6 months
measure: Tau Production Rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine
state: Missouri
Study officials:
affiliation: Washington University in Saint Louis Medical School
name: Randall Bateman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University in Saint Louis Medical School
name: Nupur Ghoshal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: