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

NCT ID: NCT06626646

Last Updated: 2024-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-10-31

Study Completion Date

2025-07-31

Brief Summary

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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

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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.

Conditions

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Peripheral Vascular Diseases Cardiovascular Disease Type 2 Diabetes Peripheral Artery Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Peripheral Artery Disease

20 patients with clinically significant/symptomatic Peripheral Artery Disease defined as symptomatic claudication and an ABI of \<0.85

No interventions assigned to this group

Control Group

20 patients who do not have Peripheral Artery Disease

No interventions assigned to this group

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Canadian Medical and Surgical Knowledge Translation Research Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Subodh Verma, MD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

David A Hess, PhD

Role: PRINCIPAL_INVESTIGATOR

Western University, Canada

Locations

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North York Diagnostic and Cardiac Centre

North York, Ontario, Canada

Site Status RECRUITING

Diagnostic Assessment Centre

Scarborough Village, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Jack Casey

Role: CONTACT

604-703-5449

Aishwarya Krishnaraj, BScH

Role: CONTACT

Facility Contacts

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Subodh Verma, MD

Role: primary

Subodh Verma, MD

Role: primary

References

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Krishnaraj A, Bakbak E, Teoh H, Pan Y, Firoz IN, Pandey AK, Terenzi DC, Verma R, Bari B, Bakbak AI, Kunjummar SP, Yanagawa B, Connelly KA, Mazer CD, Rotstein OD, Quan A, Bhatt DL, McGuire DK, Hess DA, Verma S. Vascular Regenerative Cell Deficiencies in South Asian Adults. J Am Coll Cardiol. 2024 Feb 20;83(7):755-769. doi: 10.1016/j.jacc.2023.12.012.

Reference Type BACKGROUND
PMID: 38355246 (View on PubMed)

Hess DA, Terenzi DC, Trac JZ, Quan A, Mason T, Al-Omran M, Bhatt DL, Dhingra N, Rotstein OD, Leiter LA, Zinman B, Sabongui S, Yan AT, Teoh H, Mazer CD, Connelly KA, Verma S. SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus. Cell Metab. 2019 Oct 1;30(4):609-613. doi: 10.1016/j.cmet.2019.08.015. Epub 2019 Aug 30.

Reference Type BACKGROUND
PMID: 31477497 (View on PubMed)

Hicks CW, Yang C, Ndumele CE, Folsom AR, Heiss G, Black JH 3rd, Selvin E, Matsushita K. Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study. J Am Heart Assoc. 2018 Aug 21;7(16):e008644. doi: 10.1161/JAHA.118.008644.

Reference Type BACKGROUND
PMID: 30369315 (View on PubMed)

Shishehbor MH, White CJ, Gray BH, Menard MT, Lookstein R, Rosenfield K, Jaff MR. Critical Limb Ischemia: An Expert Statement. J Am Coll Cardiol. 2016 Nov 1;68(18):2002-2015. doi: 10.1016/j.jacc.2016.04.071. Epub 2016 Sep 28.

Reference Type BACKGROUND
PMID: 27692726 (View on PubMed)

Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. doi: 10.1016/S0140-6736(13)61249-0. Epub 2013 Aug 1.

Reference Type BACKGROUND
PMID: 23915883 (View on PubMed)

Other Identifiers

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Pro00080564

Identifier Type: -

Identifier Source: org_study_id

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