Human Brain Antioxidants During Oxidative Stress

May 1, 2019 updated by: University of Minnesota

Noninvasive Antioxidant Quantification in the Human Brain Under Oxidative Stress

Antioxidants are important for having a good memory and for smart thinking when people get old, and that is important for everyone's quality of life. This research will find out if normal aging and Alzheimer's disease use up brain antioxidants. It will develop a new imaging tool that can help doctors to stop cognitive decline.

Study Overview

Status

Completed

Conditions

Detailed Description

The objective of this proposal is to advance the mission of improving the health and well-being of older Americans by augmenting ongoing dementia prevention and treatment initiatives. It undertakes research on dementia associated with both normal aging and AD. A new scientist will develop a novel and powerful human brain antioxidant assay using state-of-the art instrumentation. The approach will be translated to the clinical environment so that it can be disseminated for use with new research. Specifically, the concentrations of two important antioxidants, ascorbate (Asc) and glutathione (GSH) will be measured noninvasively in the human brain. One aim is to measure whether a recent finding of lower brain GSH concentration in the occipital cortex of cognitively normal elder subjects is also found in the posterior cingulate cortex, and whether human brain Asc homeostasis persists in both brain regions. A complementary specific aim is to determine whether lower brain GSH concentration also occurs under the oxidative stress associated with Alzheimer's disease (AD). At the same time, data measured in subjects with AD have potential to advance this powerful new technology toward discovering an early stage biomarker. A sub aim is to make this technology available to a wide range of physicians and investigators. As such, data processing will be fully automated using commercially available software. This novel noninvasive technology facilitates a paradigm shift from systemic assays to quantifying antioxidants directly in the affected brain region. The approach will take advantage of state of the art 7 T instrumentation while developing analogous methods on a clinical 3 T scanner. The process of optimizing magnetic resonance spectroscopy (MRS) for quantification of brain Asc and GSH concentrations necessitated reliable quantification of an extensive neurochemical profile (i.e. 19 brain metabolites), which includes the four compounds that are typically observed. Spectra acquired in stimulated echo acquisition mode (STEAM) will be de-convolved quantitatively into contributions from the metabolites that contribute discernable resonances using a linear combination model approach (LCModel). Reliable quantification of brain GSH and Asc concentrations will first be achieved using ultra high field MRS with multiple transmit coil technology and accompanying radiofrequency (B1) shimming, then translated to a lower field clinical platform. Successful completion will determine whether low brain glutathione concentration is widespread in the elder human brain and whether this difference is exacerbated by AD.

Study Type

Observational

Enrollment (Actual)

52

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 89 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All data have been accrued for the healthy aging aim, which included healthy people age 18-22 and age 70-89. To study the second aim, 23 patients with AD will be recruited from the Minneapolis, MN VA medical center. 23 age - and gender- matched controls will be recruited to study neurodegenerative disease associated demand on the antioxidant system. We do NOT currently have the resources to screen candidates with AD who are not current patients at the VA medical center in Minneapolis.

Description

Inclusion Criteria:

Age and gender match to AD patients: age range 65-89:

note that we anticipate that our patients will be predominantly male, so we are NOT likely to enroll females for this portion of the study

Exclusion Criteria::

Claustrophobia Implanted metal devices Pregnancy > RDA dietary supplements

≥ 5 F+V per day Smoking Depression Poor health or systemic illness Medial history of or evidence for cognitive problems Unstable medication usage Neurological problems Psychiatric disorder Substance abuse Usage of investigational drugs Inability to complete cognitive tests written in and calibrated for English speakers Inadequate vision or hearing to accommodate participation MMSE (dementia) score ≤ 26

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Elderly control
Healthy elderly subjects age and gender matched to the AD cohort, predominantly male

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antioxidant in Alzheimers
Time Frame: 1 year
Occipital cortex and posterior cingulate ascorbate and glutathione concentration in young and elder patients as well as in patients with AD
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Melissa Terpstra, PhD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

July 24, 2018

Study Registration Dates

First Submitted

October 22, 2012

First Submitted That Met QC Criteria

October 22, 2012

First Posted (Estimate)

October 25, 2012

Study Record Updates

Last Update Posted (Actual)

May 3, 2019

Last Update Submitted That Met QC Criteria

May 1, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1208M18321
  • R01AG039396 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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