Human CNS Tau Kinetics in Tauopathies

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03545126

Acronym

TANGLES

Enrollment

Registered

2018-06-04

Start date

2017-08-21

Completion date

2022-03-04

Last updated

2022-04-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Corticobasal Degeneration (CBD), Frontotemporal Dementia (FTD MAPT Mutation), Progressive Supranuclear Palsy (PSP)

Keywords

Tauopathies

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.

Interventions

OTHER13C6 Leucine

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

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Tau Fractional Turnover Rate (FTR)	6 months	Calculated by using CSF tau labeling and plasma free leucine.

Secondary

Measure	Time frame	Description
CSF Tau Absolute Concentration	6 months	Measured using labeled and unlabeled tau protein isoforms that will be immunoprecipitated and analyzed by mass spectrometry.
Tau Production Rate	6 months	Measured by FTR multiplied by CSF tau concentration.

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026