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Human CNS Tau Kinetics in Tauopathies (TANGLES)

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ClinicalTrials.gov Identifier: NCT03545126
Recruitment Status : Recruiting
First Posted : June 4, 2018
Last Update Posted : August 24, 2018
Sponsor:
Collaborators:
Association of Frontotemporal Degeneration
Tau Consortium
Information provided by (Responsible Party):
Washington University School of Medicine

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
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 Type : Observational
Estimated Enrollment : 32 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Human CNS Tau Kinetics in Tauopathies
Actual Study Start Date : August 21, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Group/Cohort 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)




Primary Outcome Measures :
  1. Tau Fractional Turnover Rate (FTR) [ Time Frame: 6 months ]
    Calculated by using CSF tau labeling and plasma free leucine.


Secondary Outcome Measures :
  1. CSF Tau Absolute Concentration [ Time Frame: 6 months ]
    Measured using labeled and unlabeled tau protein isoforms that will be immunoprecipitated and analyzed by mass spectrometry.

  2. Tau Production Rate [ Time Frame: 6 months ]
    Measured by FTR multiplied by CSF tau concentration.


Biospecimen Retention:   Samples Without DNA
Plasma CSF


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03545126


Contacts
Contact: Melissa M Sullivan 314-747-4857 m.sullivan@wustl.edu
Contact: Melody Li, MS, OTR/L 314-273-6062 slia@wustl.edu

Locations
United States, Missouri
Washington University in St. Louis School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Melissa M Sullivan    314-747-4857    m.sullivan@wustl.edu   
Contact: Melody Li, MS, OTR/L    314-273-6062    slia@wustl.edu   
Principal Investigator: Randall J Bateman, MD         
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

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03545126     History of Changes
Other Study ID Numbers: 201703052
First Posted: June 4, 2018    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided at this time.

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:
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Supranuclear Palsy, Progressive
Tauopathies
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Paralysis
Eye Diseases