ANZCTR - Registration

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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]

none

Universal Trial Number (UTN)

Trial acronym

Ex-PAD

Linked study record

Health condition

Health condition(s) or problem(s) studied:

peripheral artery disease

Condition category

Condition code

Cardiovascular

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]

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]

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]

60 minutes after infusion is commenced, at the beginning of the maximal exercise test.

Secondary outcome [1]

Microvascular blood flow will be measured in the thigh via contrast enhanced ultrasound imaging during contrast agent infusion.

Timepoint [1]

Pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.

Secondary outcome [2]

Cardiac function will be assessed via echocardiographic assessment using a commercial ultrasound machine.

Timepoint [2]

Baseline, pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.

Secondary outcome [3]

Cerebral blood flow will be measured via transcranial Doppler and duplex ultrasound.

Timepoint [3]

Baseline, pre-exercise (after 1 hour of infusion), post exercise and after 30 minutes of recovery.

Secondary outcome [4]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

University

Name [1]

Institute for Physical Activity and Nutrition, Deakin University.

Address [1]

221 Burwood Hwy, Burwood, Victoria 3125

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

University of the Sunshine Coast

Address [1]

90 Sippy Downs Drive, Sippy Downs Queensland 4556

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Deakin University Human Research Ethics Committee

Ethics committee address [1]

Melbourne Burwood Campus,
221 Burwood Highway, Burwood, VIC 3125

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/05/2022

Approval date [1]

20/06/2022

Ethics approval number [1]

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

Dr Hannah Thomas

Address

Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125

Country

Australia

Phone

+61404293441

Fax

[email protected]

Contact person for public queries

Name

Hannah Thomas

Address

Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125

Country

Australia

Phone

+61404293441

Fax

[email protected]

Contact person for scientific queries

Name

Hannah Thomas

Address

Deakin University, 221 Burwood Hwy, Burwood, Victoria 3125

Country

Australia

Phone

+61404293441

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

No
No IPD sharing reason/comment: Participant privacy

What supporting documents are/will be available?

Doc. No.	Type	Attachment
17636	Study protocol	Study-related document.pdf
17637	Informed consent form	Study-related document.pdf
17638	Ethical approval	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.

Trial Review

Documents added manually

Documents added automatically