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

Diabetes Clinical Trial

— ORIGINS-RCE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05253521
• Other study ID #: Pro00059664
• Status: Completed
• Start date: January 8, 2022
• Est. completion date: January 18, 2023

Study information

• Verified date: February 2023
• Source: Canadian Medical and Surgical Knowledge Translation Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 18, 2023
• Est. primary completion date: January 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Diabetes
• Diabetes Mellitus
• Heart Diseases
• Ischemia
• Ischemic Heart Disease
• Ischemic Stroke
• Myocardial Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Type 1 Diabetes
• Type 2 Diabetes
• Vascular Diseases

Locations

Country	Name	City	State
Canada	Markham HealthPlex Medical Centre	Markham	Ontario
Canada	North York Diagnostic and Cardiac Centre	North York	Ontario
Canada	Diagnostic Assessment Centre	Scarborough	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Canadian Medical and Surgical Knowledge Translation Research Group	Unity Health Toronto, Western University, Canada

Country where clinical trial is conducted

Canada, 

References & Publications (14)

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: CMAJ 1999 Sep 7;161(5):489. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Circulation. 2018 Jul 31;138(5):e76. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the concentration of serum oxidative stress markers individuals of South Asian origins and White individuals of European origins		Baseline
Other	Changes in the concentration of serum inflammatory markers individuals of South Asian origins and White individuals of European origins		Baseline
Primary	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	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
Secondary	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