Peripheral Artery Disease (D058729)NCT05648630
Improving Exercise Rehabilitation Efficacy Outcomes Veterans Peripheral Artery Disease
A study testing PB125 and Exercise Rehabilitation in people with Peripheral Artery Disease (D058729) and Oxidative Stress (D018384), run by VA Office of Research and Development at 2 sites in United States.
Trial summary
Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Peripheral Artery Disease (D058729), Oxidative Stress (D018384), Inflammation (D007249)
- What is being tested?
- PB125 and Exercise Rehabilitation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Jul 2023to 1 Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 40 and older with clinically diagnosed femoropopliteal PAD (ankle-brachial index < 0.9)
- Must understand the study requirements and be willing and able to sign an informed consent document
- Patients with mild cognitive impairment (i.e., montreal cognitive assessment (MOCA) <26) will be included but must have a responsible caregiver or spouse present during the informed consent
- Women that are not pregnant, breastfeeding, or likely to become pregnant within the next 6 months
Who cannot join
- Patients with a bleeding disorder that would contraindicate the performance of a muscle biopsy, such as a history of clinically significant bleeding diathesis (i.e., Hemophilia A or B, Von Willebrand's Disease, or congenital Factor VII deficiency)
- Patients with a complex atherosclerotic lesion such that withholding medication creates disproportionate risk
- Women currently taking hormone replacement therapy
- Any other condition or event considered exclusionary by the PI and faculty physician
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Utah Dept of Vascular Surgery
Salt Lake City, Utah, 84132
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001
About this study
Official title: Improving Exercise Rehabilitation Efficacy and Outcomes in Veterans With Peripheral Artery Disease: Targeting Oxidative Stress and Inflammation
Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. The proposed project will comprehensively examine the novel strategy of Nuclear Factor Erythroid-2-like 2 (Nrf2) activation using PB125, aimed at diminishing oxidative stress and inflammation, and thereby lessening the negative impacts of the disease. This therapeutic will be evaluated in isolation and in combination with exercise rehabilitation to determine if there is a complimentary benefit. The ultimate goal is to provide insight into a potential novel therapeutic treatment for this disease, therefore, improving exercise tolerance and quality of life in this growing population.
Read the detailed description
Peripheral artery disease (PAD) is a debilitating atherosclerotic disease caused by plaque development in the arteries leading to diminished skeletal muscle blood flow, oxygen delivery, and metabolic dysfunction during ambulation causing marked exercise intolerance. Veterans have a disproportionate risk of developing PAD compared to the general population because of higher levels of smoking, hypertension, diabetes, and obesity. Worryingly, the mortality rate for PAD in Veterans (~30%) is nearly double that of the general population. Currently, the best treatment of PAD is exercise rehabilitation, however, issues with patient motivation and pain reduce the effectiveness of this treatment. There is a pressing, and unmet need to identify the sites and underlying mechanisms of the systemic dysfunction leading to exercise intolerance induced by PAD. Oxidative stress and inflammation play important roles in the development and progression of PAD. Critically, the peripheral vasculature (diminished blood flow) and mitochondria (diminished respiration) are primary determinants/mechanisms responsible for exercise intolerance in health and disease that are particularly vulnerable to elevations in oxidative stress and inflammation, making these likely sites of systemic dysfunction leading to exercise intolerance in Veterans with PAD. Any vascular or mitochondrial dysfunction would further augment oxidative stress and inflammation initiating a vicious cycle. It is the central hypothesis that increased endogenous antioxidant capacity and diminished inflammation will improve oxygen delivery and utilization during exercise, thus, increasing the efficacy of exercise rehabilitation due to increased adherence and exercise capacity. To test this hypothesis, the investigators will utilize the naturally-derived Nuclear Factor Erythroid-2-like 2 (Nrf2; the "master regulator of antioxidant enzymes") activator, PB125, to stimulate induction of endogenous antioxidants and decrease the activity of inflammatory pathways. Veterans with PAD will be randomly assigned to receive either PB125 or Placebo supplementation. Each Veteran will undergo three phases of testing: 1) baseline, 2) post 1 month of supplement loading, and 3) post 12 weeks of exercise rehabilitation with continued supplementation. Functional capacity and cognitive function (Aim 1), Vascular function and exercising hemodynamics (Aim 2), and in vivo and ex vivo mitochondrial respiration (Aim 3) will be assessed each phase. Monthly assessments of functional capacity, behavioral regulation, quality of life, and physical activity will track improvements across the trial. At the conclusion of these studies, the investigators will have expanded the knowledge of the mechanisms underlying exercise intolerance in Veterans suffering from PAD, and, more importantly from a clinical perspective, provided insight into a potential novel therapeutic treatment to improve exercise rehabilitation efficacy for this population. It is anticipated this advancement will contribute to advancing clinical practice in rehabilitative medicine, and ultimately, improving the quality of life for Veterans living with PAD.
- Being tested
- PB125, Placebo, Exercise Rehabilitation
- Keywords
- inflammation (D007249), Skeletal muscle (D018482), Antioxidants (D000975)
- Medical subject headings
- Peripheral Arterial Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PB125Dietary supplement
PB125 is a naturally-derived plant-based supplement that activates the Nuclear Factor Erythroid-2-like 2 (Nrf2) system to stimulate induction of endogenous antioxidants and anti-inflammatory pathways.
PlaceboDietary supplement
A placebo will be used in combination with exercise rehabilitation allowing for a double blinded placebo controlled design.
Exercise RehabilitationBehavioural
A 12-week treadmill based supervised rehabilitation
| Study group | Role | What they receive |
|---|---|---|
| Exercise Rehabilitation+PB125 | Experimental | Participants will be assigned to the Exercise+Placebo or Exercise+PB125 rehabilitation interventions using block randomization. Receives: Dietary Supplement: PB125; Behavioral: Exercise Rehabilitation |
| Exercise Rehabilitation with Placebo | Placebo comparator | Participants will be assigned to the Exercise+Placebo rehabilitation interventions using block randomization. Receives: Dietary Supplement: Placebo; Behavioral: Exercise Rehabilitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six-minute Walk Test (6MWT) Change
6MWT will be quantified with total distance, last minute speed, and claudication onset time. Greater distance and higher speed indicates better functional capacity and greater change over time suggests improvement.
Measured: Baseline, month 1, month 2, month 3, month 4
Exercise pressor response (EPR) Change
EPR will be quantified with the change in mean arterial blood pressure from rest to exercise. A greater EPR indicates elevated cardiovascular risk and a reduction in the EPR over time suggests improvement.
Measured: Baseline, month 1, month 2, month 3, month 4
Intramuscular maximal bioenergetics (Vmax) Change
Vmax will be quantified as the rate of intramuscular phosphocreatine replenishment following exercise. A greater Vmax indicates better mitochondrial and hemodynamic function and greater change over time suggests improvement.
Measured: Baseline, month 1, month 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2022
- Study start3 Jul 2023
- Primary completion1 Oct 2025
- Study completion1 Oct 2025
Why it stopped: Inadequate participant recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Artery Disease (D058729)Studies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two separate groups of subjects (patients with PAD) receiving PB125 or Placebo
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- David W. Wray, PhD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05648630
- Sponsor's protocol ID
- E3913-W
- Other IDs
- RX003913
- Status last verified
- Nov 2025
- First submitted
- 4 Nov 2022
- Last updated
- 10 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Upon written request, a limited, de-identified, anonymized dataset will be created pursuant to the Data Use Agreement. This DUA will limit the use of the dataset and prohibit the recipient from taking steps to identify individuals whose data is included in the dataset. This dataset will be provided through a password-protected, machine-readable database format. Whenever possible, the dataset will be delivered through physical transfer of the storage medium.
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Exercise Rehabilitation Efficacy and Outcomes in Veterans With Peripheral Artery Disease: Targeting Oxidative Stress and Inflammation
- ClinicalTrials.gov ID
- NCT05648630
- Acronym / sponsor ID
- E3913-W
- Keywords
- inflammation (D007249), Skeletal muscle (D018482), Antioxidants (D000975)
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inadequate participant recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 3 Jul 2023 (actual)
- Primary completion
- 1 Oct 2025 (actual)
- Study completion
- 1 Oct 2025 (actual)
- First posted
- 13 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. The proposed project will comprehensively examine the novel strategy of Nuclear Factor Erythroid-2-like 2 (Nrf2) activation using PB125, aimed at diminishing oxidative stress and inflammation, and thereby lessening the negative impacts of the disease. This therapeutic will be evaluated in isolation and in combination with exercise rehabilitation to determine if there is a complimentary benefit. The ultimate goal is to provide insight into a potential novel therapeutic treatment for this disease, therefore, improving exercise tolerance and quality of life in this growing population.
Detailed description
Peripheral artery disease (PAD) is a debilitating atherosclerotic disease caused by plaque development in the arteries leading to diminished skeletal muscle blood flow, oxygen delivery, and metabolic dysfunction during ambulation causing marked exercise intolerance. Veterans have a disproportionate risk of developing PAD compared to the general population because of higher levels of smoking, hypertension, diabetes, and obesity. Worryingly, the mortality rate for PAD in Veterans (~30%) is nearly double that of the general population. Currently, the best treatment of PAD is exercise rehabilitation, however, issues with patient motivation and pain reduce the effectiveness of this treatment. There is a pressing, and unmet need to identify the sites and underlying mechanisms of the systemic dysfunction leading to exercise intolerance induced by PAD. Oxidative stress and inflammation play important roles in the development and progression of PAD. Critically, the peripheral vasculature (diminished blood flow) and mitochondria (diminished respiration) are primary determinants/mechanisms responsible for exercise intolerance in health and disease that are particularly vulnerable to elevations in oxidative stress and inflammation, making these likely sites of systemic dysfunction leading to exercise intolerance in Veterans with PAD. Any vascular or mitochondrial dysfunction would further augment oxidative stress and inflammation initiating a vicious cycle. It is the central hypothesis that increased endogenous antioxidant capacity and diminished inflammation will improve oxygen delivery and utilization during exercise, thus, increasing the efficacy of exercise rehabilitation due to increased adherence and exercise capacity. To test this hypothesis, the investigators will utilize the naturally-derived Nuclear Factor Erythroid-2-like 2 (Nrf2; the "master regulator of antioxidant enzymes") activator, PB125, to stimulate induction of endogenous antioxidants and decrease the activity of inflammatory pathways. Veterans with PAD will be randomly assigned to receive either PB125 or Placebo supplementation. Each Veteran will undergo three phases of testing: 1) baseline, 2) post 1 month of supplement loading, and 3) post 12 weeks of exercise rehabilitation with continued supplementation. Functional capacity and cognitive function (Aim 1), Vascular function and exercising hemodynamics (Aim 2), and in vivo and ex vivo mitochondrial respiration (Aim 3) will be assessed each phase. Monthly assessments of functional capacity, behavioral regulation, quality of life, and physical activity will track improvements across the trial. At the conclusion of these studies, the investigators will have expanded the knowledge of the mechanisms underlying exercise intolerance in Veterans suffering from PAD, and, more importantly from a clinical perspective, provided insight into a potential novel therapeutic treatment to improve exercise rehabilitation efficacy for this population. It is anticipated this advancement will contribute to advancing clinical practice in rehabilitative medicine, and ultimately, improving the quality of life for Veterans living with PAD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two separate groups of subjects (patients with PAD) receiving PB125 or Placebo
| Arm | Type | Receives |
|---|---|---|
| Exercise Rehabilitation+PB125 | Experimental | Dietary Supplement: PB125, Behavioral: Exercise RehabilitationParticipants will be assigned to the Exercise+Placebo or Exercise+PB125 rehabilitation interventions using block randomization. |
| Exercise Rehabilitation with Placebo | Placebo comparator | Dietary Supplement: Placebo, Behavioral: Exercise RehabilitationParticipants will be assigned to the Exercise+Placebo rehabilitation interventions using block randomization. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 40 and older with clinically diagnosed femoropopliteal PAD (ankle-brachial index < 0.9)
- Must understand the study requirements and be willing and able to sign an informed consent document
- Patients with mild cognitive impairment (i.e., montreal cognitive assessment (MOCA) <26) will be included but must have a responsible caregiver or spouse present during the informed consent
- Women that are not pregnant, breastfeeding, or likely to become pregnant within the next 6 months
Key exclusion criteria (4 listed)
- Patients with a bleeding disorder that would contraindicate the performance of a muscle biopsy, such as a history of clinically significant bleeding diathesis (i.e., Hemophilia A or B, Von Willebrand's Disease, or congenital Factor VII deficiency)
- Patients with a complex atherosclerotic lesion such that withholding medication creates disproportionate risk
- Women currently taking hormone replacement therapy
- Any other condition or event considered exclusionary by the PI and faculty physician
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PB125PB125 is a naturally-derived plant-based supplement that activates the Nuclear Factor Erythroid-2-like 2 (Nrf2) system to stimulate induction of endogenous antioxidants and anti-inflammatory pathways. | Dietary supplement | Exercise Rehabilitation+PB125 |
| PlaceboA placebo will be used in combination with exercise rehabilitation allowing for a double blinded placebo controlled design. | Dietary supplement | Exercise Rehabilitation with Placebo |
| Exercise RehabilitationA 12-week treadmill based supervised rehabilitation | Behavioural | Exercise Rehabilitation with Placebo, Exercise Rehabilitation+PB125 |
Primary outcome
Six-minute Walk Test (6MWT) Change
Time frame: Baseline, month 1, month 2, month 3, month 4
6MWT will be quantified with total distance, last minute speed, and claudication onset time. Greater distance and higher speed indicates better functional capacity and greater change over time suggests improvement.
Exercise pressor response (EPR) Change
Time frame: Baseline, month 1, month 2, month 3, month 4
EPR will be quantified with the change in mean arterial blood pressure from rest to exercise. A greater EPR indicates elevated cardiovascular risk and a reduction in the EPR over time suggests improvement.
Intramuscular maximal bioenergetics (Vmax) Change
Time frame: Baseline, month 1, month 4
Vmax will be quantified as the rate of intramuscular phosphocreatine replenishment following exercise. A greater Vmax indicates better mitochondrial and hemodynamic function and greater change over time suggests improvement.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
- Individual participant dataSharing planned: No. Upon written request, a limited, de-identified, anonymized dataset will be created pursuant to the Data Use Agreement. This DUA will limit the use of the dataset and prohibit the recipient from taking steps to identify individuals whose data is included in the dataset. This dataset will be provided through a password-protected, machine-readable database format. Whenever possible, the dataset will be delivered through physical transfer of the storage medium.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David W. Wray, PhD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PB125 and Exercise Rehabilitation in people with Peripheral Artery Disease (D058729) and Oxidative Stress (D018384), run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six-minute Walk Test (6MWT) Change (time frame: Baseline, month 1, month 2, month 3, month 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2025.