Human Brain Antioxidants During Oxidative Stress

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by University of Minnesota - Clinical and Translational Science Institute
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute Identifier:
First received: October 22, 2012
Last updated: April 2, 2015
Last verified: April 2015

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.

Oxidative Stress
Antioxidant Capacity
Alzheimer's Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Noninvasive Antioxidant Quantification in the Human Brain Under Oxidative Stress

Resource links provided by NLM:

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Antioxidant in Alzheimers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Occipital cortex and posterior cingulate ascorbate and glutathione concentration in young and elder patients as well as in patients with AD

Estimated Enrollment: 86
Study Start Date: June 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Healthy human subjects in the age range 18-22
Healthy elderly subjects
Patients with Alzheimer's disease
Elderly control
Healthy elderly subjects age matched to the AD cohort

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 cigulate 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.


Ages Eligible for Study:   18 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

In the first phase of this project, images and spectra will be obtained by enrolling 4 healthy adults who have given informed consent for validation of methodological development. To study normal aging, 18 healthy young (age 18 - 22 years old) and 18 healthy elder (age 70 -89 years old) subjects will be enrolled. To study the second aim, 23 patients with AD and 23 age - matched controls will be enrolled to study neurodegenerative disease associated demand on the antioxidant system.


Inclusion Criteria:

  • Inclusion criteria for age in years:

Technical development: 18 or older Young Aim 1: 18-22 Elder Aim 1: 70-89 Elder Aim 2: Age match to AD patients who range 65-89

Inclusion criteria for patients with AD Consensus diagnosis mild to moderate AD on file MMSE 18-26

Exclusion Criteria:

  • Exclusion criteria all Claustrophobia Implanted metal devices Pregnancy

Exclusion criteria for all except the 4 subjects participating in technical development > RDA dietary supplements

≥ 5 F+V per day Smoking Depression (score < 22 for young, < 14 for elder) 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 Except for patients with AD: MMSE (dementia) score ≤ 26

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01713816

Contact: Melissa J Terpstra, PhD 612-625-4927

United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Melissa Terpstra    612-625-4927      
Principal Investigator: Melissa Terpstra         
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Melissa Terpstra, PhD    612-625-4927   
Contact: Michelle Hartwig    612-626-2001      
Principal Investigator: Melissa Terpstra, PhD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Melissa Terpstra, PhD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute Identifier: NCT01713816     History of Changes
Other Study ID Numbers: 1208M18321, R01AG039396
Study First Received: October 22, 2012
Last Updated: April 2, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Alzheimer's disease
Magnetic Resonance Spectroscopy

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents processed this record on September 01, 2015