Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000014651
Ethics application status
Approved
Date submitted
15/11/2022
Date registered
9/01/2023
Date last updated
9/01/2023
Date data sharing statement initially provided
9/01/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of antioxidants on health and exercise ability in individuals with peripheral artery disease.
Scientific title
The effects of antioxidants on vascular function and exercise capacity in peripheral artery disease.
Secondary ID [1] 308416 0
none
Universal Trial Number (UTN)
Trial acronym
Ex-PAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
peripheral artery disease 328221 0
Condition category
Condition code
Cardiovascular 325269 325269 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 324872 0
Treatment: Other
Comparator / control treatment
The control group will undergo the same intervention with a saline placebo infusion (sodium chloride 0.9% - normal saline 500mL IV freeflex bag).
Control group
Placebo

Outcomes
Primary outcome [1] 333127 0
Cardiorespiratory fitness/exercise capacity.

Cardiopulmonary exercise test: Participants will undergo a graded exercise test to exhaustion on a cycle ergometer to determine exercise capacity using standard clinical exercise testing and indirect calorimetry equipment.
Timepoint [1] 333127 0
60 minutes after infusion is commenced, at the beginning of the maximal exercise test.
Secondary outcome [1] 415906 0
Microvascular blood flow will be measured in the thigh via contrast enhanced ultrasound imaging during contrast agent infusion.
Timepoint [1] 415906 0
Pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.
Secondary outcome [2] 417261 0
Cardiac function will be assessed via echocardiographic assessment using a commercial ultrasound machine.
Timepoint [2] 417261 0
Baseline, pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.
Secondary outcome [3] 417262 0
Cerebral blood flow will be measured via transcranial Doppler and duplex ultrasound.
Timepoint [3] 417262 0
Baseline, pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.
Secondary outcome [4] 417263 0
Femoral arterial diameter and blood velocity will be assessed using 2D and Doppler ultrasound imaging. This will be assessed as a composite outcome.
Timepoint [4] 417263 0
Baseline, pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.

Eligibility
Key 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.
Minimum age
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
block randomization
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Randomized, cross over, placebo-controlled trial.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/01/2023
Actual
Date of last participant enrolment
Anticipated
1/12/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 312669 0
University
Name [1] 312669 0
Institute for Physical Activity and Nutrition, Deakin University.
Country [1] 312669 0
Australia
Primary sponsor type
University
Name
Institute for Physical Activity and Nutrition, Deakin University.
Address
221 Burwood Hwy, Burwood, Victoria 3125
Country
Australia
Secondary sponsor category [1] 314611 0
None
Name [1] 314611 0
Address [1] 314611 0
Country [1] 314611 0
Other collaborator category [1] 282489 0
University
Name [1] 282489 0
University of the Sunshine Coast
Address [1] 282489 0
90 Sippy Downs Drive, Sippy Downs Queensland 4556
Country [1] 282489 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311972 0
Deakin University Human Research Ethics Committee
Ethics committee address [1] 311972 0
Melbourne Burwood Campus,
221 Burwood Highway, Burwood, VIC 3125
Ethics committee country [1] 311972 0
Australia
Date submitted for ethics approval [1] 311972 0
27/05/2022
Approval date [1] 311972 0
20/06/2022
Ethics approval number [1] 311972 0
2022-153

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123018 0
Dr Hannah Thomas
Address 123018 0
Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125
Country 123018 0
Australia
Phone 123018 0
+61404293441
Fax 123018 0
Email 123018 0
h.thomas@deakin.edu.au
Contact person for public queries
Name 123019 0
Dr Hannah Thomas
Address 123019 0
Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125
Country 123019 0
Australia
Phone 123019 0
+61404293441
Fax 123019 0
Email 123019 0
h.thomas@deakin.edu.au
Contact person for scientific queries
Name 123020 0
Dr Hannah Thomas
Address 123020 0
Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125
Country 123020 0
Australia
Phone 123020 0
+61404293441
Fax 123020 0
Email 123020 0
h.thomas@deakin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant privacy


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17636Study protocol    384990-(Uploaded-06-01-2023-16-25-05)-Study-related document.pdf
17637Informed consent form    384990-(Uploaded-06-01-2023-16-25-20)-Study-related document.pdf
17638Ethical approval    384990-(Uploaded-15-11-2022-16-56-36)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.