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

Completed

• Conditions: Diabetes; Type 2 Diabetes; Ischemic Heart Disease; Ischemic Stroke; Peripheral Vascular Diseases; Type 1 Diabetes; Cardiovascular Diseases

• Registration Number: NCT05253521
• Lead Sponsor: Canadian Medical and Surgical Knowledge Translation Research Group

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-01-07
• Study Start: 2022-01-08
• Study First Submitted QC: 2022-02-12
• Study First Posted: 2022-02-23
• Primary Completion: 2023-01-18
• Study Completion: 2023-01-18
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-08
• Last Update Posted: 2023-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

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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)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The change in the frequency / absolute number of circulating ALDHhiSSChi granulocyte precursor cells between individuals of South Asian origins and White individuals of European origin	Baseline

Secondary Outcome Measures

Name	Time	Method
The change in the frequency / absolute number of circulating ALDHhiSSCmid precursor cells with monocytes/macrophage phenotype between individuals of South Asian origins and White individuals of European origin	Baseline
The change in the frequency / absolute number of circulating ALDHhiSSClo cells with primitive provascular progenitor cell phenotype between individuals of South Asian origins and White individuals of European origin	Baseline

Trial Locations

Locations (3)

Markham HealthPlex Medical Centre; 🇨🇦 Markham, Ontario, Canada

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

Diagnostic Assessment Centre; 🇨🇦 Scarborough, Ontario, Canada