The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion

NCT ID: NCT05253521

Last Updated: 2023-02-09

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

COMPLETED

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-01-08

Study Completion Date

2023-01-18

Brief Summary

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ORIGINS-RCE is an observational, cross-sectional, two-arm study aimed at determining if an individual's ethnic origin influences the number of blood vessel-forming stem cells in the bloodstream. Circulating progenitor cells will be enumerated and the distribution patterns of these cell types will be assessed to determine if these parameters differ between individuals of South Asian origin and European origin. Specifically, this study will evaluate if differential regenerative cell exhaustion (RCE) may account, at least in part, for the differences in cardiovascular risk reported between individuals of South Asian vs European origin.

Detailed Description

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Individuals of South Asian origins have been reported to be at higher risk of ischemic heart disease than those of European origins. While differential morphometries and culturally related behavioural habits are believed to account in part for the difference, there is growing evidence that cardiometabolic risk factors can accelerate pro-vascular progenitor cell depletion and dysfunction. The cumulative effects that aberrant regenerative cell exhaustion (RCE) have on vessel repair accordingly increases the risk of atherothrombotic events.

ORIGINS-RCE is an observational, cross-sectional, two-arm study that will evaluate the progenitor cell profiles of peripheral blood samples from 120 individuals (60 of South Asian origins, 60 of European origins). The working hypothesis is that individuals of South Asian and European origins have innately different progenitor profiles that can be further altered by behavioural/cultural habits. The resultant differences in RCE capability will affect the balance between pro-inflammatory and vessel repair functions that in turn contribute to the contrasting cardiometabolic risks exhibited between the two study cohorts.

Conditions

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Diabetes Type 1 Diabetes Type 2 Diabetes Ischemic Heart Disease Ischemic Stroke Cardiovascular Diseases Peripheral Vascular Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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South Asian Origin

Individuals who identify as having Anglo-Indian, Bangladeshi, Bengali, Bhutanese, Goan, Gujarati, Indian, Jatt, Kashmiri, Maharashtrian, Malayali, Nepali, Pakistani, Punjabi, Sindhi, Sinhalese, Sri Lankan, Tamil, Telugu, or other South Asian origin

No interventions assigned to this group

White Individuals of European Origin

Individuals who identify as having western European, other northern European, southern European, eastern European or other European origin

No interventions assigned to this group

Eligibility Criteria

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Exclusion Criteria

1. Severe congestive heart failure (as defined by New York Heart Association - class IV)
2. Any life-threatening disease expected to result in death within the next 2 years
3. Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening.
4. Known severe liver disease
5. White blood cell count ≥15 x 10\^9/L
6. Active infectious disease requiring antibiotic or anti-viral agents
7. Known acquired immunodeficiency syndrome such as HIV
8. On oral steroid therapy (e.g. prednisone or other corticosteroids) or other immunosuppressive agents (e.g. methotrexate)
9. Treated autoimmune disorder (excluding type 1 diabetes)
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Unity Health Toronto

OTHER

Sponsor Role collaborator

Western University, Canada

OTHER

Sponsor Role collaborator

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, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

David A Hess, PhD

Role: PRINCIPAL_INVESTIGATOR

Western University, Canada

Locations

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Markham HealthPlex Medical Centre

Markham, Ontario, Canada

Site Status

North York Diagnostic and Cardiac Centre

North York, Ontario, Canada

Site Status

Diagnostic Assessment Centre

Scarborough Village, Ontario, Canada

Site Status

Countries

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Canada

References

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Sheth T, Nair C, Nargundkar M, Anand S, Yusuf S. Cardiovascular and cancer mortality among Canadians of European, south Asian and Chinese origin from 1979 to 1993: an analysis of 1.2 million deaths. CMAJ. 1999 Jul 27;161(2):132-8.

Reference Type BACKGROUND
PMID: 10439820 (View on PubMed)

Misra A, Wasir JS, Pandey RM. An evaluation of candidate definitions of the metabolic syndrome in adult Asian Indians. Diabetes Care. 2005 Feb;28(2):398-403. doi: 10.2337/diacare.28.2.398.

Reference Type BACKGROUND
PMID: 15677799 (View on PubMed)

Volgman AS, Palaniappan LS, Aggarwal NT, Gupta M, Khandelwal A, Krishnan AV, Lichtman JH, Mehta LS, Patel HN, Shah KS, Shah SH, Watson KE; American Heart Association Council on Epidemiology and Prevention; Cardiovascular Disease and Stroke in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Stroke Council. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018 Jul 3;138(1):e1-e34. doi: 10.1161/CIR.0000000000000580. Epub 2018 May 24.

Reference Type BACKGROUND
PMID: 29794080 (View on PubMed)

McKeigue PM, Miller GJ, Marmot MG. Coronary heart disease in south Asians overseas: a review. J Clin Epidemiol. 1989;42(7):597-609. doi: 10.1016/0895-4356(89)90002-4.

Reference Type BACKGROUND
PMID: 2668448 (View on PubMed)

Cubbon RM, Murgatroyd SR, Ferguson C, Bowen TS, Rakobowchuk M, Baliga V, Cannon D, Rajwani A, Abbas A, Kahn M, Birch KM, Porter KE, Wheatcroft SB, Rossiter HB, Kearney MT. Human exercise-induced circulating progenitor cell mobilization is nitric oxide-dependent and is blunted in South Asian men. Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):878-84. doi: 10.1161/ATVBAHA.109.201012. Epub 2010 Jan 28.

Reference Type BACKGROUND
PMID: 20110574 (View on PubMed)

Putman DM, Liu KY, Broughton HC, Bell GI, Hess DA. Umbilical cord blood-derived aldehyde dehydrogenase-expressing progenitor cells promote recovery from acute ischemic injury. Stem Cells. 2012 Oct;30(10):2248-60. doi: 10.1002/stem.1206.

Reference Type BACKGROUND
PMID: 22899443 (View on PubMed)

Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, Eades WC, Creer MH, Nolta JA. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood. 2006 Mar 1;107(5):2162-9. doi: 10.1182/blood-2005-06-2284. Epub 2005 Nov 3.

Reference Type BACKGROUND
PMID: 16269619 (View on PubMed)

Putman DM, Cooper TT, Sherman SE, Seneviratne AK, Hewitt M, Bell GI, Hess DA. Expansion of Umbilical Cord Blood Aldehyde Dehydrogenase Expressing Cells Generates Myeloid Progenitor Cells that Stimulate Limb Revascularization. Stem Cells Transl Med. 2017 Jul;6(7):1607-1619. doi: 10.1002/sctm.16-0472. Epub 2017 Jun 15.

Reference Type BACKGROUND
PMID: 28618138 (View on PubMed)

Terenzi DC, Trac JZ, Teoh H, Gerstein HC, Bhatt DL, Al-Omran M, Verma S, Hess DA. Vascular Regenerative Cell Exhaustion in Diabetes: Translational Opportunities to Mitigate Cardiometabolic Risk. Trends Mol Med. 2019 Jul;25(7):640-655. doi: 10.1016/j.molmed.2019.03.006. Epub 2019 Apr 30.

Reference Type BACKGROUND
PMID: 31053416 (View on PubMed)

Balber AE. Concise review: aldehyde dehydrogenase bright stem and progenitor cell populations from normal tissues: characteristics, activities, and emerging uses in regenerative medicine. Stem Cells. 2011 Apr;29(4):570-5. doi: 10.1002/stem.613.

Reference Type BACKGROUND
PMID: 21308868 (View on PubMed)

Gentry T, Foster S, Winstead L, Deibert E, Fiordalisi M, Balber A. Simultaneous isolation of human BM hematopoietic, endothelial and mesenchymal progenitor cells by flow sorting based on aldehyde dehydrogenase activity: implications for cell therapy. Cytotherapy. 2007;9(3):259-74. doi: 10.1080/14653240701218516.

Reference Type BACKGROUND
PMID: 17464758 (View on PubMed)

Shoulars K, Noldner P, Troy JD, Cheatham L, Parrish A, Page K, Gentry T, Balber AE, Kurtzberg J. Development and validation of a rapid, aldehyde dehydrogenase bright-based cord blood potency assay. Blood. 2016 May 12;127(19):2346-54. doi: 10.1182/blood-2015-08-666990. Epub 2016 Mar 11.

Reference Type BACKGROUND
PMID: 26968535 (View on PubMed)

Murphy C, Kanaganayagam GS, Jiang B, Chowienczyk PJ, Zbinden R, Saha M, Rahman S, Shah AM, Marber MS, Kearney MT. Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men. Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):936-42. doi: 10.1161/01.ATV.0000258788.11372.d0. Epub 2007 Jan 25.

Reference Type BACKGROUND
PMID: 17255539 (View on PubMed)

Terenzi DC, Bakbak E, Trac JZ, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Isolation and characterization of circulating pro-vascular progenitor cell subsets from human whole blood samples. STAR Protoc. 2021 Feb 1;2(1):100311. doi: 10.1016/j.xpro.2021.100311. eCollection 2021 Mar 19.

Reference Type BACKGROUND
PMID: 33554145 (View on PubMed)

Park B, Krishnaraj A, Teoh H, Bakbak E, Dennis F, Quan A, Hess DA, Verma S. GLP-1RA therapy increases circulating vascular regenerative cell content in people living with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2024 Aug 1;327(2):H370-H376. doi: 10.1152/ajpheart.00257.2024. Epub 2024 Jun 14.

Reference Type DERIVED
PMID: 38874618 (View on PubMed)

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 DERIVED
PMID: 38355246 (View on PubMed)

Other Identifiers

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Pro00059664

Identifier Type: -

Identifier Source: org_study_id

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