Oxidative Stress Links Aging, Activity, and Mobility Limitation

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT01177189
• Collaborator: University of Utah (Other)
• Enrollment: 87
• Arms: 2
• Actual Duration (Months): 72.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aging	Dietary Supplement: Vitamins C, E, and alpha lipoic acid	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Participants will consume either a daily oral antioxidant cocktail or a placebo. The oral antioxidant cocktail consists of vitamin C, vitamin E, and alpha lipoic acid.Participants will consume either a daily oral antioxidant cocktail or a placebo. The oral antioxidant cocktail consists of vitamin C, vitamin E, and alpha lipoic acid.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Oxidative Stress Links Aging, Activity and Mobility Limitation
• Actual Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jul 3, 2017
• Actual Study Completion Date: Jul 3, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Vascular Function (i.e. % Flow Mediated Vasodilation) [8 weeks]

   The effect on flow mediated vasodilation is measured using Doppler ultrasound.

Secondary Outcome Measures

1. Exercise-induced Oxidative Stress (i.e. Free Radical Concentrations and Levels of Lipid Peroxidation) [8 weeks]

   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.

2. Vascular Function Following the Antioxidant Intervention [8 weeks]

   The degree of vasodilation following the antioxidant intervention measured by Doppler ultrasound.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• VA Office of Research and Development
• University of Utah

Investigators

• Principal Investigator: Russell S Richardson, PhD, VA Salt Lake City Health Care System, Salt Lake City, UT

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 30, 2017

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01177189
• Other Study ID Numbers: E6910-R
• First Posted: Aug 6, 2010
• Last Update Posted: Feb 21, 2019
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by VA Office of Research and Development: Oxidative Stress; Free radicals; Aging
• Additional relevant MeSH terms: Mobility Limitation; Ascorbic Acid; Thioctic Acid

Study Results

Participant Flow

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily
Period Title: Overall Study
STARTED	42	45
COMPLETED	42	45
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Total of all reporting groups
Overall Participants	42	45	87
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	42 100%	0 0%	42 48.3%
>=65 years	0 0%	45 100%	45 51.7%
Sex: Female, Male (Count of Participants)
Female	21 50%	17 37.8%	38 43.7%
Male	21 50%	28 62.2%	49 56.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	42 100%	45 100%	87 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily
Measure Participants	42	45
Mean (Standard Error) [percentage of vasodilation]	7.4 (0.6)	5.2 (0.4)

2. Secondary Outcome

Title	Exercise-induced Oxidative Stress (i.e. Free Radical Concentrations and Levels of Lipid Peroxidation)
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily
Measure Participants	42	45
Mean (Standard Error) [units on a scale]	1.51 (0.19)	2.7 (0.13)

3. Secondary Outcome

Title	Vascular Function Following the Antioxidant Intervention
Description	The degree of vasodilation following the antioxidant intervention measured by Doppler ultrasound.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily	Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily
Measure Participants	42	45
Mean (Standard Error) [percentage of vasodilation]	5.8 (0.6)	8.2 (0.6)

Adverse Events

Time Frame	4 years
Arm/Group Title	Arm 1		Arm 2
Arm/Group Description	Young healthy men and women aged 18-30 Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily		Older healthy men and women aged >70. Vitamins C, E, and alpha lipoic acid: Oral antioxidant cocktail or placebo to be consumed daily
All Cause Mortality
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/45 (0%)
Serious Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/45 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/45 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.