Vascular Regenerative Cell Exhaustion in Adults with Peripheral Artery Disease (PAD-VRCE)

Recruiting

• Conditions: Peripheral Vascular Diseases; Cardiovascular Disease; Type 2 Diabetes; Peripheral Artery Disease

• Registration Number: NCT06626646
• Lead Sponsor: Canadian Medical and Surgical Knowledge Translation Research Group

Brief Summary

PAD-VRCE is an observational, cross-sectional, two arm study aimed at determining if the presence of peripheral artery disease (PAD) can influence the number of circulating regenerative cells in blood. From peripheral blood samples, circulating progenitor cell content will be assessed via flow cytometry and compared between individuals with PAD and individuals without PAD. Ultimately, this study plans to evaluate the relationship between PAD, vascular regenerative cell exhaustion and overall cardiovascular health.

Detailed Description

Individuals with peripheral artery disease (PAD) have been shown to have poorer cardiovascular health outcomes than the general population. It is believed that the number of people living with PAD is greatly underestimated and furthermore, mortality due to the most severe form of PAD - critical limb ischemia - is increasing. There is a growing body of evidence that the presence of cardiovascular risk factors leads to the imbalance of circulating regenerative cells. The aggregate impact of this regenerative cell exhaustion phenotype is an increased risk of adverse events and progression of disease states.

PAD-VRCE is an observational, cross-sectional, two-arm cohort study aimed at determining the differences in the progenitor cell profiles in the blood of individuals with PAD in comparison to individuals without PAD. We hypothesize that people with PAD will exhibit depleted levels of these progenitor cells defined as vascular regenerative cell exhaustion. VRCE impacts the function of anti-inflammatory cells and associated repair mechanisms within blood vessels, and may contribute to the differential long term outcomes between the two groups.

Study Timeline

• Status Verified: 2024-10
• Study Start: 2024-10
• Study First Submitted: 2024-10-02
• Study First Submitted QC: 2024-10-02
• Last Update Submitted: 2024-10-02
• Study First Posted: 2024-10-04
• Last Update Posted: 2024-10-04
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Adults ≥18 and ≤80 years of age who meet either of the following criteria:

   1. Clinically significant/symptomatic PAD (defined as symptomatic claudication with and an ankle brachial index of less than 0.85).
   2. No history of PAD.

2. Willing and able to provide written informed consent and comply with study procedures.

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Exclusion Criteria

1. Unable or unwilling to provide written informed consent or to provide a peripheral blood sample.
2. Any life-threatening disease expected to result in death within two years.
3. Any malignancy not considered cured (except basal cell carcinoma of the skin). An individual is considered cured if there has been no evidence of cancer recurrence for the five years prior to screening.
4. Uncontrolled hypertension.
5. New York Heart Association Class IV heart failure.
6. Active liver disease or liver dysfunction.
7. Active kidney disease or kidney dysfunction.
8. History of hemorrhagic stroke or other major bleeding disorder.
9. White blood cell count of ≥15x10^9/L.
10. Active infectious disease requiring systemic antibiotic or anti-viral agents.
11. Known acquired immunodeficiency syndrome, such as Human Immunodeficiency Virus.
12. On oral steroid therapy (e.g. prednisone or other corticosteroids) or other immunosuppressive agents (e.g. methotrexate).
13. Treated autoimmune disorders

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The difference in the frequency / absolute number of circulating primitive myeloid progenitor cells (ALDHhiSSClow) between individuals with PAD and without PAD	Baseline

Secondary Outcome Measures

Name	Time	Method
The difference in the amount of intracellular reactive oxygen species produced by ALDHhi progenitor cell subsets in individuals with PAD and without PAD	Baseline
The difference in the levels of circulating inflammatory and oxidative stress markers in individuals with PAD and without PAD	Baseline
The difference in the frequency /absolute count of ALDHhiSSCmid monocytes in individuals with PAD or without PAD	Baseline

Trial Locations

Locations (2)

North York Diagnostic and Cardiac Centre; 🇨🇦 North York, Ontario, Canada

Diagnostic Assessment Centre; 🇨🇦 Scarborough, Ontario, Canada