Exercise in Health and Chronic Obstructive Pulmonary Disease

NCT ID: NCT02300064

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 185 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2016-05-31

Brief Summary

The purpose of this study is to find out more about the effects of chronic obstructive pulmonary disease (COPD) on the function of blood vessels, the heart, and muscle at rest and during exercise.

Detailed Description

Oxidative stress, defined as an imbalance between pro and antioxidant molecular species in favor of the former, has recently been recognized as a potential mechanism in the peripheral muscle dysfunction associated with COPD. a series of studies are proposed to better understand the role and source of oxidative stress in the skeletal muscle of patients with COPD. Specifically, three main aims will address the following questions regarding COPD, skeletal muscle, and oxidative stress: where is oxidative stress most prevalent, why does oxidative stress occur, and what are the consequences of oxidative stress in COPD? the overall hypothesis to be tested is that COPD results in a shift toward greater intramuscular oxidative stress and this is, at least in part, responsible for the diminished mechanical efficiency and greater peripheral muscle fatiguability during muscular work often associated with this disease. The vascular consequence of this augmented free radical load is altered vascular function and a disruption of the local matching of perfusion and metabolism in skeletal muscle during exercise. These crucial changes result in a cascade of factors such as local hypoxia and elevated vascular shear stress, entering a vicious cycle that leads to the generation of more free radicals, especially during physical work. It is proposed that this imbalance between pro and antioxidant potential, toward oxidative stress, plays a significant role in the attenuated exercise capacity and reduced muscle fatigue resistance associated with COPD.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy volunteers

Healthy volunteers will undergo one or more exercise interventions: knee-extensor exercise test; exercise test with restricting/releasing blood flow; exercise test with variable oxygen concentration and MRI; or exercise test with oral antioxidant or placebo cocktail.

Group Type: EXPERIMENTAL

Knee-extensor exercise test

Intervention Type: OTHER

Steady-state, single leg knee-extensor exercise at 20 Watts for 10 minutes

Exercise test with restricting/releasing blood flow

Intervention Type: OTHER

10 minute submaximal (20 Watts) single leg knee-extensor exercise with blood flow clamped 10-15% lower by arterial infustion of phenylephrine; 10 minute passive single leg knee-extensor exercise with blood flow matched to the 20 Watt work rate level by arterial adenosine infusion; 10 minute seated rest with blood flow matched to the 20 Watt work rate level by adenosine infusion. Each test separated by at least 30 minutes rest.

Exercise test with variable oxygen concentration and MRI

Intervention Type: OTHER

Two bouts of single leg knee-extensor exercise to maximal effort breathing regular air (21% oxygen) or 100% oxygen through a mouthpiece, with a 90 minute rest period between each bout. The same experiment performed again on a separate day in an magnetic resonance imaging (MRI) machine

Exercise test with oral antioxidant or placebo cocktail

Intervention Type: OTHER

Antioxidants (Vitamin E - 400 international units, Vitamin C - 1000 milligrams and Alpha lipoic acid - 600 milligrams) or matching placebo capsules administered orally followed by femoral nerve stimulation and single leg knee-extensor exercise for 30 minutes at 50% maximum effort

COPD patients

Patients with Chronic Obstructive Pulmonary Disease (COPD) will undergo one or more exercise interventions: knee-extensor exercise test; exercise test with restricting/releasing blood flow; exercise test with variable oxygen concentration and MRI; or exercise test with oral antioxidant or placebo cocktail.

Group Type: EXPERIMENTAL

Knee-extensor exercise test

Intervention Type: OTHER

Steady-state, single leg knee-extensor exercise at 20 Watts for 10 minutes

Exercise test with restricting/releasing blood flow

Intervention Type: OTHER

10 minute submaximal (20 Watts) single leg knee-extensor exercise with blood flow clamped 10-15% lower by arterial infustion of phenylephrine; 10 minute passive single leg knee-extensor exercise with blood flow matched to the 20 Watt work rate level by arterial adenosine infusion; 10 minute seated rest with blood flow matched to the 20 Watt work rate level by adenosine infusion. Each test separated by at least 30 minutes rest.

Exercise test with variable oxygen concentration and MRI

Intervention Type: OTHER

Two bouts of single leg knee-extensor exercise to maximal effort breathing regular air (21% oxygen) or 100% oxygen through a mouthpiece, with a 90 minute rest period between each bout. The same experiment performed again on a separate day in an magnetic resonance imaging (MRI) machine

Exercise test with oral antioxidant or placebo cocktail

Intervention Type: OTHER

Antioxidants (Vitamin E - 400 international units, Vitamin C - 1000 milligrams and Alpha lipoic acid - 600 milligrams) or matching placebo capsules administered orally followed by femoral nerve stimulation and single leg knee-extensor exercise for 30 minutes at 50% maximum effort

Interventions

Knee-extensor exercise test

Steady-state, single leg knee-extensor exercise at 20 Watts for 10 minutes

Intervention Type: OTHER

Exercise test with restricting/releasing blood flow

10 minute submaximal (20 Watts) single leg knee-extensor exercise with blood flow clamped 10-15% lower by arterial infustion of phenylephrine; 10 minute passive single leg knee-extensor exercise with blood flow matched to the 20 Watt work rate level by arterial adenosine infusion; 10 minute seated rest with blood flow matched to the 20 Watt work rate level by adenosine infusion. Each test separated by at least 30 minutes rest.

Intervention Type: OTHER

Exercise test with variable oxygen concentration and MRI

Two bouts of single leg knee-extensor exercise to maximal effort breathing regular air (21% oxygen) or 100% oxygen through a mouthpiece, with a 90 minute rest period between each bout. The same experiment performed again on a separate day in an magnetic resonance imaging (MRI) machine

Intervention Type: OTHER

Exercise test with oral antioxidant or placebo cocktail

Antioxidants (Vitamin E - 400 international units, Vitamin C - 1000 milligrams and Alpha lipoic acid - 600 milligrams) or matching placebo capsules administered orally followed by femoral nerve stimulation and single leg knee-extensor exercise for 30 minutes at 50% maximum effort

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Chronic Obstructive Pulmonary Disease (COPD) patients (over 18 years old) and
• age-matched healthy controls (over 18 years old)

Exclusion Criteria

• Severe Chronic Obstructive Pulmonary Disease (volume exhaled at the end of the first section of forced expiration is predicted to be under 30 percent),
• Severe Heart Failure

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Russell Richardson

Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Russell Richardson, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

US Department of Veterans Affairs

Locations

Veterans Affairs Salt Lake City Heath Care System

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

32404

Identifier Type: -

Identifier Source: org_study_id