TANGLES: Human CNS Tau Kinetics in Tauopathies

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT03545126
• Collaborator: Association of Frontotemporal Degeneration (Other), Tau Consortium (Other)
• Enrollment: 27
• Location: 1
• Actual Duration (Months): 54.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Progressive Supranuclear Palsy (PSP); Corticobasal Degeneration (CBD); Frontotemporal Dementia (FTD MAPT Mutation)	Other: 13C6 Leucine

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 27 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Human CNS Tau Kinetics in Tauopathies
• Actual Study Start Date: Aug 21, 2017
• Actual Primary Completion Date: Mar 4, 2022
• Actual Study Completion Date: Mar 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Progressive Supranuclear Palsy (PSP) N=12 Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling.	Other: 13C6 Leucine; Recruited participants will be given 13C6-labeled leucine through intravenous infusion (4mg/kg/hr for 16hrs)
Corticobasal Degeneration (CBD) N=8 Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling.	Other: 13C6 Leucine; Recruited participants will be given 13C6-labeled leucine through intravenous infusion (4mg/kg/hr for 16hrs)
Frontotemporal Dementia: MAPT N=12 Family members with or at-risk of tau mutations (e.g. P301L) Age: 18 and older Recruited participants will be given 13C6 Leucine through intravenous infusion (4mg/kg/hr for 16hrs), and CSF will be collected five times over 120 days (on approximately days 1-4, 5-10, 11-20, 21-60 and 61-120) after labeling.	Other: 13C6 Leucine; Recruited participants will be given 13C6-labeled leucine through intravenous infusion (4mg/kg/hr for 16hrs)

Outcome Measures

Primary Outcome Measures

1. Tau Fractional Turnover Rate (FTR) [6 months]

   Calculated by using CSF tau labeling and plasma free leucine.

Secondary Outcome Measures

1. CSF Tau Absolute Concentration [6 months]

   Measured using labeled and unlabeled tau protein isoforms that will be immunoprecipitated and analyzed by mass spectrometry.

2. Tau Production Rate [6 months]

   Measured by FTR multiplied by CSF tau concentration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University in St. Louis School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Association of Frontotemporal Degeneration
• Tau Consortium

Investigators

• Principal Investigator: Randall Bateman, MD, Washington University in Saint Louis Medical School
• Principal Investigator: Nupur Ghoshal, MD, PhD, Washington University in Saint Louis Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03545126
• Other Study ID Numbers: 201703052
• First Posted: Jun 4, 2018
• Last Update Posted: Apr 13, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Washington University School of Medicine: Tauopathies
• Additional relevant MeSH terms: Supranuclear Palsy, Progressive; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Tauopathies

Study Results

No Results Posted as of Apr 13, 2022