None listed
Conditions
Brief summary
Peripheral artery disease (PAD) can result in extensive functional alterations including vascular dysfunction, reduced capacity to exercise, and reduced quality of life. The progression and cause of PAD is thought to be associated with increased oxidative stress and tissue injury related to increased production of reactive oxygen species (ROS) and a decrease in antioxidant defenses. Oxidative stress and inflammation are major features in the development of atherosclerosis and are therefore extremely relevant in the development of PAD. Several important enzymatic antioxidant defenses have been shown to be deficient in the muscle of PAD individuals compared to controls. Endogenous antioxidants function as defenses to remove or regulate ROS production. Therefore, antioxidant deficiencies can lead to a state of excess oxidative stress which contributes to vascular dysfunction, decreased exercise capacity, and the development of PAD, cardiovascular disease, and cerebrovascular disease. However, few studies have adequately explored antioxidant treatment in PAD patients, and none have explored antioxidant treatment and the effects on the extensive vascular network during exercise. The aims of this developmental work are to directly test whether antioxidant treatment (via the intravenous infusion of an antioxidant) can acutely improve vascular function and exercise capacity in patients with PAD.
Interventions
Intravenous infusion of an antioxidant glutathione will be performed on one occasion. Rate of infusion will be 15 mg/min over 4 hours (approximately 3600mg). The infusion will be ongoing during the exercise test.
Outcome measures will be measured at baseline, after 1 hour of infusion (pre-exercise), immediately post an acute exercise bout and 30 minutes after exercise.
These measures will be conducted in the Exercise Science Laboratory at Deakin University, Burwood by research staff who are memb
Intravenous infusion of an antioxidant glutathione will be performed on one occasion. Rate of infusion will be 15 mg/min over 4 hours (approximately 3600mg). The infusion will be ongoing during the exercise test. Outcome measures will be measured at baseline, after 1 hour of infusion (pre-exercise), immediately post an acute exercise bout and 30 minutes after exercise. These measures will be conducted in the Exercise Science Laboratory at Deakin University, Burwood by research staff who are members of the research team and are trained in cannulation and first aid. The exercise bout will be a single maximal exercise test performed on a treadmill in a one-on-one scenario. This exercise will be performed approximately 60 minutes after the infusion is commenced. The exercise test will be supervised by a minimum of two first aid trained and experienced research team members. The test is completed at 3.2 km/h and begins at a grade of 0% for the first 5 minutes and then is increased by 3.5% every 3 minutes until subjects reach their maximum exercise capacity. Alternatively, we will use the graded Gardner-Skinner treadmill exercise test which is a well-accepted modified-load treadmill exercise test that is frequently used in randomized trials of therapeutic interventions in PAD. In this protocol, participants begin walking on the treadmill at 2.0 mph with a grade of zero. The treadmill speed is maintained at 2.0 mph throughout testing, and the treadmill grade is increased by 2% every 2 minutes. Participants with PAD who are unable to walk at 2.0 mph should perform a modified Gardner treadmill test in which the speed begins at 0.5 mph and a grade of zero and speed is increased by 0.5 mph every 2 minutes until 2.0 mph is achieved. When a speed of 2.0 mph is reached, the treadmill grade is increased by 2% every 2 minutes. Participants are asked to continue walking as long as possible until ischemic leg symptoms, fatigue, or other symptoms prevent them from continuing. A minimum of one week washout will separate the two trial sessions (intervention and control session). The entire testing sessions will be supervised by two members of the research team.
Sponsors
Institute for Physical Activity and Nutrition, Deakin University.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: Aged 40-75 y, BMI less than or equal to 35 kg/m2, ankle brachial index (ABI) of less than or equal to 0.90.
Exclusion criteria
Exclusion Criteria: History of myocardial infarction, stroke, dementia, or respiratory disease, non-cardiovascular barriers to exercise, critical limb ischemia or foot ulcers, identification of any medical condition requiring immediate therapeutic intervention and/or current or previous smoker (within the last 12 months).
Outcome results
None listed