Human CNS Tau Kinetics in Tauopathies

Progressive Supranuclear Palsy (PSP) Clinical Trial

— TANGLES  

Official title:

Human CNS Tau Kinetics in Tauopathies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03545126
• Other study ID #: 201703052
• Status: Completed
• Start date: August 21, 2017
• Est. completion date: March 4, 2022

Study information

• Verified date: April 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 4, 2022
• Est. primary completion date: March 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Aß or medications thought to influence Aß production or clearance rates (benzodiazepines, muscarinic agents, or anti-epileptics)

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Corticobasal Degeneration (CBD)
• Frontotemporal Dementia
• Frontotemporal Dementia (FTD MAPT Mutation)
• Pick Disease of the Brain
• Progressive Supranuclear Palsy (PSP)
• Supranuclear Palsy, Progressive
• Tauopathies

Intervention

Other:
• 13C6 Leucine
Recruited participants will be given 13C6-labeled leucine through intravenous infusion (4mg/kg/hr for 16hrs)

Locations

Country	Name	City	State
United States	Washington University in St. Louis School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	Association of Frontotemporal Degeneration, Tau Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tau Fractional Turnover Rate (FTR)	Calculated by using CSF tau labeling and plasma free leucine.	6 months
Secondary	CSF Tau Absolute Concentration	Measured using labeled and unlabeled tau protein isoforms that will be immunoprecipitated and analyzed by mass spectrometry.	6 months
Secondary	Tau Production Rate	Measured by FTR multiplied by CSF tau concentration.	6 months