CNS Tau Kinetics in Healthy Aging and Alzheimer's Disease

NCT03938870 | Completed DMC

• 1 other identifier: 201502091
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Alzheimer's disease (AD) is the most common cause of dementia and currently has no disease modifying treatments or simple accurate diagnostic tests. The goal of this project is to study how tau (a protein thought to cause AD) is made, transported and cleared in the human body. Better understanding of these processes may lead to improved understanding of AD, earlier diagnosis and a way to evaluate treatment.

Conditions

Alzheimer's Disease; Brain Diseases; Central Nervous System Diseases; Delirium, Dementia, Amnestic, Cognitive Disorders; Dementia; Mental Disorders; Nervous System Diseases; Neurodegenerative Diseases; Tauopathies

Keywords

Alzheimer's Disease; Alzheimer's; biomarker; dementia; Tau; Tau Kinetics; Tauopathies

Outcome Measures

Primary Outcomes (1)

• Tau kinetics in cerebrospinal fluid [half-life of tau], as assessed by tau stable isotope labeling kinetics (SILK) method

  To measure physiological tau kinetics with the tau SILK method in the CNS of human participants.

  4 months

Secondary Outcomes (3)

• Age

  4 months

• Tau aggregation measured by PET Imaging

  4 months

• Amyloid aggregation measured by PET Imaging

  4 months

Study Arms (3)

Experimental: Group 1

30 Young Normal Controls(YNC) ages 18 \& Older will enroll to evaluate leucine infusion methods of labeling, vs. the oral method. They will have 5 lumbar punctures (LPs) and the amount of labeled tau in the CSF will be analyzed to obtain tau kinetics in human central nervous system (CNS).

Other: L-Leucine 13C6

Experimental: Group 2

Group 30 CDR \> 0. There will be collection of CSF and blood. The participants will either be labeled by intravenous infusion method with leucine or oral method based off the results from the Young Normal Control Group. They will have 5 lumbar punctures (LPs) and the amount of labeled tau in the CSF will be analyzed to obtain tau kinetics in human central nervous system (CNS).

Other: L-Leucine 13C6

Experimental: Group 3

Group of 40 CDR = 0 Age Matched. There will be collection of CSF and blood. The participants will either be labeled by intravenous infusion method with leucine or oral method based off the results from the Young Normal Control Group. They will have 5 lumbar punctures (LPs) and the amount of labeled tau in the CSF will be analyzed to obtain tau kinetics in human central nervous system (CNS).

Other: L-Leucine 13C6

Interventions

L-Leucine 13C6 OTHER

Experimental: Group 1; Experimental: Group 2; Experimental: Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will recruit 100 participants (age 18+) 30 Young Normal Controls, 30 AD participants (age 65+) and 40 age-matched controls (age 65+) to participate in this study. Studies will be conducted at the Clinical Trials Research Unit at Washington University School of Medicine. Volunteers will be screened for any major medical abnormalities, bleeding risks, or any other reason they might not tolerate the procedure. The participants will either be labeled by intravenous infusion method or oral method. They will have 5 lumbar punctures (LPs) and the amount of labeled tau in the CSF will be analyzed to obtain tau kinetics in human central nervous system (CNS).

You may qualify if:

• Males or females of any race aged 18 or older
• No evidence of a neurologic disorder or traumatic head injury by history or examination
• Able to take food and drink by mouth safely
• Participants must be able to provide informed consent

You may not qualify if:

• Requires tube feeding for nutrition and/or hydration
• Already on a special diet (e.g. Gluten free)
• History of bleeding disorder
• Allergy to Lidocaine
• Pregnancy
• Any contraindication for lumbar puncture e.g. blood thinners

Sponsors & Collaborators

• Washington University School of Medicine: lead
• BrightFocus Foundation: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Washington University in Saint Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Bateman RJ, Munsell LY, Morris JC, Swarm R, Yarasheski KE, Holtzman DM. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med. 2006 Jul;12(7):856-61. doi: 10.1038/nm1438. Epub 2006 Jun 25.

  PMID: 16799555 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and Cerebrospinal Fluid

MeSH Terms

Conditions

Alzheimer Disease; Brain Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Dementia; Mental Disorders; Nervous System Diseases; Neurodegenerative Diseases; Tauopathies; Pick Disease of the Brain

Condition Hierarchy (Ancestors)

Frontotemporal Dementia; Frontotemporal Lobar Degeneration

Study Officials

• Randall Bateman, MD

  Washington University in Saint Louis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2015
• First Posted: May 6, 2019
• Study Start: August 18, 2015
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: February 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)