The Role of South Asian vs European Origins on Circulating Regenerative Cell Exhaustion (ORIGINS-RCE)

February 8, 2023 updated by: Canadian Medical and Surgical Knowledge Translation Research Group
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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Markham, Ontario, Canada, L3S0A2
        • Markham HealthPlex Medical Centre
      • North York, Ontario, Canada, M6B1N6
        • North York Diagnostic and Cardiac Centre
      • Scarborough, Ontario, Canada, M1S4N6
        • Diagnostic Assessment Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants will be identified from primary care and cardiology outpatient clinics in the Greater Toronto Area using paper-based and electronic medical records.

Description

  1. Adults 40 years of age or older of South Asian origin or white European origin as defined by the following:

    1. South Asian defined as any individual who identifies as 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.
    2. White Europeans or European Origin defined as any individual who identifies as from western European, other northern European, southern European, eastern European or other European origins.
  2. Willing and able to provide written informed consent and comply with study requirements.

  3. Must meet criteria of one of the two following groups:

    1. Established diabetes (HbA1c ≤10.5%) with no CVD but meets 1 or more of the following criteria:

      • On insulin therapy
      • Cigarette smoker or stopped smoking within 3 months
      • Documented hypertension (as defined by a sitting blood pressure at screening of ≥130/80 mmHg) OR currently on antihypertensive therapy
      • History of treated or untreated dyslipidemia
      • High sensitivity C-reactive protein ≥2.0 mg/L
      • eGFR 30 to 60 mL/min/1.73m^2
      • Documented micro- or macro-albuminuria

    2. Established CVD and meets 1 or more of the following criteria within 10 years prior to screening:

      • Documented coronary artery disease (CAD)
      • Documented cerebrovascular or carotid disease
      • Documented peripheral artery disease (PAD)

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
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
White Individuals of European Origin
Individuals who identify as having western European, other northern European, southern European, eastern European or other European origin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Baseline
Baseline

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Baseline
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
Time Frame: Baseline
Baseline

Other Outcome Measures

Outcome Measure
Time Frame
Changes in the concentration of serum oxidative stress markers individuals of South Asian origins and White individuals of European origins
Time Frame: Baseline
Baseline
Changes in the concentration of serum inflammatory markers individuals of South Asian origins and White individuals of European origins
Time Frame: Baseline
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Canadian Medical and Surgical Knowledge Translation Research Group

Collaborators

Unity Health Toronto
Western University, Canada

Investigators

  • Principal Investigator: David A Hess, PhD, Western University, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 8, 2022

Primary Completion (ACTUAL)

January 18, 2023

Study Completion (ACTUAL)

January 18, 2023

Study Registration Dates

First Submitted

January 7, 2022

First Submitted That Met QC Criteria

February 12, 2022

First Posted (ACTUAL)

February 23, 2022

Study Record Updates

Last Update Posted (ESTIMATE)

February 9, 2023

Last Update Submitted That Met QC Criteria

February 8, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00059664

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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