Clinical trial NCT06769347: Circulating Vascular Regenerative Cell Exhaustion in Individuals Without Type 2 Diabetes Who Are of South Asian or European Origins
Official title: Circulating Vascular Regenerative Cell Exhaustion in Individuals Without Type 2 Diabetes Who Are of South Asian or European Origins
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiovascular Diseases Risk
Keywords: Progenitor Cells
Cardiometabolic Risk
Ethnic Origins
Lead sponsor: Canadian Medical and Surgical Knowledge Translation Research Group
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: Western University, Canada
First posted: 2025-01-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

Brief summary: ORIGINS-VRCE-2 is an observational study aimed to assess how blood vessel forming stem cells from individuals without diabetes or a history of cardiovascular disease differ between individuals of South Asian and European ethnicities. The overarching objective of the study is to investigate whether differential vessel reparative stem cell populations and characteristics may underlie the elevated cardiovascular risk observed among South Asian individuals compared to individuals of European origins.

Detailed description: Cardiovascular diseases (CVD) are the main cause of death worldwide. Notably, individuals of South Asian (SA) origin have 3 to 5-fold increased rates of CVD compared to European individuals, which cannot be entirely explained by diet, lifestyle, or socioeconomic factors. Therefore, the mechanisms driving the increased CVD risk in SA individuals remains largely unknown.

Cardiovascular health is maintained by vascular regenerative cells, which secrete pro-vascular cytokines involved in various pro-angiogenic, arteriogenic and vasculogenic pathways. It has been shown that SA adults with type 2 diabetes or CVD show vascular regenerative cell exhaustion (VRCE), characterized by a reduced number or dysfunction of pro-vascular cells compared to European adults with type 2 diabetes or CVD. Thus, VRCE presents as a novel mechanism to explain the increased cardiovascular risk SA individuals experience. However, it is unclear whether VRCE only occurs in people with cardiometabolic diseases, or if it is a phenomenon that is also present in healthy SA individuals.

ORIGINS-VRCE-2 is an observational, two-armed, cross-sectional study that will enroll 60 healthy South Asian and 60 healthy European individuals. Vascular regenerative cells will be isolated from peripheral blood samples for enumeration and characterization.

Eligibility criteria: Inclusion Criteria:

1. Adults 18 years of age or older of South Asian origin or European origin as defined by the following: i. 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 origins. ii. European Origin defined as any individual who identifies as from western Europe, northern Europe, southern Europe, eastern Europe or other European origins.
2. Willing and able to provide written informed consent and comply with study requirements
3. Must fulfill the following exclusion criteria:

Exclusion Criteria:

1. No previous diagnosis of type 2 diabetes
2. Any previous CV events such as:

   1. Prior myocardial infarction
   2. Coronary revascularization
   3. Coronary artery disease, peripheral artery disease, cerebrovascular disease
3. Any life-threatening disease expected to result in death within the next 2 years
4. 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
5. Known severe liver disease (e.g. Non-alcoholic fatty liver disease, chronic liver disease, liver cirrhosis, etc.)
6. White blood cell count ≥ 15 x 10\^9/L
7. Active infectious disease requiring antibiotic or anti-viral agents
8. Known acquired immunodeficiency syndrome such as HIV
9. On oral steroid therapy (e.g. prednisone) or other immunosuppressive agents (e.g. methotrexate)
10. Treated autoimmune disorder

Primary outcomes:
measure: The differences in the frequency / absolute number of circulating ALDHhi primitive progenitor cells co-expressing CD133 between individuals of South Asian origins and European origins
timeFrame: Baseline
Secondary outcomes:
measure: The differences in the frequency / absolute number of circulating ALDHhiSSCmid precursor cells with monocytes/macrophage phenotype between individuals of South Asian origins and European origin
timeFrame: Baseline
Other outcomes:
measure: Difference in the amount of intracellular reactive oxygen species (ROS) production in ALDHhi progenitor cell subsets in individuals of South Asian origins and European origins
timeFrame: Baseline
measure: Difference in the levels of inflammatory and oxidative stress biomarkers in individuals of South Asian origins and European origins
timeFrame: Baseline
Locations:
city: Markham
country: Canada
facility: Markham HealthPlex Medical Centre
state: Ontario
city: North York
country: Canada
facility: North York Diagnostic and Cardiac Centre
state: Ontario
city: North York
country: Canada
facility: Marlee Medical Centre
state: Ontario
city: Scarborough
country: Canada
facility: Diagnostic Assessment Centre
state: Ontario
city: Woodbridge
country: Canada
facility: Langstaff Medical Centre
state: Ontario
Study officials:
References:
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