Oxidative Stress Links Aging, Activity, and Mobility Limitation

Oxidative Stress Links Aging, Activity and Mobility Limitation

The purpose of this study is to understand why and how oxidative stress negatively impacts mobility in the elderly, and to determine whether antioxidant supplements can increase vascular health and mobility.

Study Overview

• Status: Terminated
• Conditions: Aging
• Intervention / Treatment: Dietary supplement: Vitamins C, E, and alpha lipoic acid

Detailed Description

With the premise that U.S. Veteran demographics reveal an aging population with significant mobility limitation and oxidative stress is tightly linked to both of these characteristics, a series of skeletal muscle/vascular studies are proposed. Specifically, in a series of recent studies the investigators' group has documented positive vascular consequences of antioxidant supplementation during exercise in older subjects that negatively impacted young people. Further provocative findings revealed that following exercise training the older subjects were now also negatively impacted by the antioxidant supplementation. These findings have implications for the understanding of the complex balance between the positive effects of exercise-based rehabilitation, exercise induced oxidative stress, aging, frailty, and subsequent mobility limitation. Therefore four specific aims are proposed that will answer the questions of where (I) oxidative stress is most prevalent in the elderly, why (II) oxidative stress occurs in the elderly, what (III) are the acute consequences of oxidative stress in the elderly, and finally how (IV) can exercise-induced oxidative stress as the result of exercise training in elderly be appropriately managed with exogenous antioxidant therapy to promote compliance and the positive outcome of increased mobility.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women aged either between 18 - 30 years (young group) and >70 years (old group)
• Free of overt disease. Subjects will be non-obese (BMI < 30) and have plasma glucose concentrations < 7.0 mmol/L under fasting conditions and < 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
• Subjects will be sedentary, defined here as no regular physical activity for at least the prior 2 years
• Candidates must have no orthopedic limitations that would prohibit them from performing cycle or knee-extensor exercise
• All women will be postmenopausal (either natural or surgical) defined as a cessation of menses for at least 2 years, and in women without a uterus, follicle stimulating hormone (FSH) > 40 IU/L

Exclusion Criteria:

• Candidates demonstrating dyslipidemia based on the National Cholesterol Education Program Guidelines of plasma total cholesterol > 240 mg/dl with LDL-cholesterol > 160 mg/dl will be excluded from participation
• Candidates who smoke or are taking medications (blood pressure medications, statins, antioxidants etc.) that could influence the results of the study will not be eligible
• In terms of diet, subjects will be asked to maintain a dietary record for one week prior to the pre-screening and if this reveals a diet that differs substantially from the "typical" average diet in both the young and old, the subject will not be eligible
• Women currently taking hormone replacement therapy (HRT) in the preceding year will be excluded from the proposed studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm 1; Young healthy men and women aged 18-30	Dietary supplement: Vitamins C, E, and alpha lipoic acid; Oral antioxidant cocktail or placebo to be consumed daily
Other: Arm 2; Older healthy men and women aged >70.	Dietary supplement: Vitamins C, E, and alpha lipoic acid; Oral antioxidant cocktail or placebo to be consumed daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular Function (i.e. % Flow Mediated Vasodilation)	The effect on flow mediated vasodilation is measured using Doppler ultrasound.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise-induced Oxidative Stress (i.e. Free Radical Concentrations and Levels of Lipid Peroxidation)	Free radicals and levels of lipid peroxidation were measured using electron paramagnetic spectroscopy and ELISA assays. A minimum value is 0 and a maximum value is 10. A higher value is a worse outcome.	8 weeks
Vascular Function Following the Antioxidant Intervention	The degree of vasodilation following the antioxidant intervention measured by Doppler ultrasound.	8 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: University of Utah
• Investigators: Principal Investigator: Russell S Richardson, PhD, VA Salt Lake City Health Care System, Salt Lake City, UT

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): July 3, 2017
• Study Completion (Actual): July 3, 2017

Study Registration Dates

• First Submitted: July 30, 2010
• First Submitted That Met QC Criteria: August 5, 2010
• First Posted (Estimate): August 6, 2010

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: October 9, 2018
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Oxidative Stress; Aging; Free radicals
• Additional Relevant MeSH Terms: Mobility Limitation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Thioctic Acid; Ascorbic Acid
• Other Study ID Numbers: E6910-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No