Diabetes Mellitus, Type 2FIERCENCT06108388
Functional Investigation of Endothelial Function and Regenerative Cell Exhaustion
An observational study of Diabetes Mellitus, Type 2, run by Canadian Medical and Surgical Knowledge Translation Research Group at 1 site in Canada.
Trial summary
FIERCE is an observational cross-sectional study. Approximately 90 individuals living with type 2 diabetes (T2D) and/or individuals living without diabetes will be randomized (2:1). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- How many people
- 90 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2023to Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Participants will be identified from primary care clinics in the Greater Toronto Area using paper-based and electronic medical records.
Who may be able to join
- Adults ≥18 years of age.
- Willing to provide written informed consent.
- Documented history of T2D
- No documented history of diabetes
Who cannot join
- Unable or unwilling to provide written informed consent or provide a peripheral blood sample.
- Any life-threatening disease expected to result in death within two years of consent.
- Any malignancy not considered cured (except basal cell carcinoma of the skin). An individual is considered cured if there has been no evidence of cancer recurrence for the five years prior to screening.
- Known severe liver disease.
- White blood cell count ≥15 x 10^9/L.
- Active infectious disease requiring systemic antibiotic or anti-viral agents.
Show all 9Show fewer
- Known acquired immunodeficiency syndrome such as HIV.
- Treated autoimmune disorders (e.g. T1D and LADA).
- On oral steroid therapy (e.g. prednisone or other corticosteroids) or other immunosuppressive agents (e.g. methotrexate).
Trial locations and contacts
1 site in 1 country.
Canada1 site
Diagnostic Assessment Centre
Scarborough Village, Ontario, M1S4N6
Subodh Verma, MD, PhD
About this study
Official title: Functional Investigation of Endothelial Function and Regenerative Cell Exhaustion in Type 2 Diabetes
FIERCE is an observational cross-sectional study. Approximately 90 individuals living with type 2 diabetes (T2D) and/or individuals living without diabetes will be randomized (2:1).
The primary objective of this trial is to determine if there are differences in the content and function of circulating vascular regenerative (VR) progenitor cell subsets isolated from individuals living with T2D versus individuals not living with T2D. The main question this study aims to answer is: Does T2D compromise or enhance VR cell functionality?
Each participant will be asked to provide a single blood sample. Blood samples will be processed to enumerate the number of vessel-repairing cells and determine the functionality of the different subtypes of vessel-repairing cells.
Read the detailed description
Type 2 diabetes (T2D) is a significant and prevalent global health concern. Individuals diagnosed with T2D are at an elevated risk of developing atherosclerotic cardiovascular (CV) disease, a leading cause of global morbidity and mortality.
Blood vessel homeostasis plays a central role in the status of CV health. Circulating vascular regenerative (VR) progenitor cells, which mediate the endogenous processes of angiogenesis, vasculogenesis, and arteriogenesis, are critical in orchestrating vessel repair. In T2D, chronic hyperglycemia and concomitant oxidative stress create a maladaptive environment that impairs vessel repair. T2D can lead to a chronic state known as vascular regenerative cell exhaustion (VRCE), characterized by the depletion of, and dysfunction in, circulating VR progenitor cells. The available data indicate that VRCE associated with T2D can lead to VR cell dysfunction and compromised vascular repair.
The investigators have developed a multi-parametric flow cytometry assay to measure VR progenitor cell content in blood samples. This assay utilizes the cytosolic detoxification enzyme aldehyde dehydrogenase (ALDH), which is highly expressed in progenitor cells from hematopoietic, endothelial, and mesenchymal stromal cell lineages. This enzyme protects progenitor cells from oxidative damage that is driven by reactive oxygen species. ALDH activity is reduced by up to 100-fold as progenitor cells differentiate towards more expendable effector cells. As such, the investigators identify cells with high or low ALDH activity in combination with cell surface markers to distinguish progenitor cell subsets (ALDHhi) from more differentiated progeny (ALDHlow). Used in conjunction with 'side scatter' (SSC), a parameter that correlates with the granularity or complexity of a cell, this assay can distinguish between and quantify ALDHhiSSClow hematopoietic/endothelial precursor cells, ALDHhiSSCmid monocytes, and ALDHhiSSChi granulocyte precursors. Previously, bone marrow-derived ALDHhiSSClow cells were shown to co-express the primitive cell markers CD34 and CD133 and exhibit multipotent hematopoietic colony-forming ability in vitro. In the immunodeficient NOD/SCID mouse model of hindlimb ischemia, transplantation of ALDHhiSSClow cells into the ischemic limb led to improved muscle perfusion recovery. The potential of this cell therapy to prevent amputations in individuals with critical limb ischemia has been evaluated in clinical trial settings.
The peripheral blood of individuals living with T2D for >10-years exhibits a depletion of ALDHhiSSClow VR progenitor cells, lower frequencies of ALDHhiSSCmid monocytes with vessel reparative function, and an increased frequency of ALDHhiSSChi inflammatory granulocyte precursors compared to that from individuals not living with T2D. The VRCE phenotype was partially reversed in people living with T2D and established coronary artery disease (CAD) after they had been on the SGLT2 inhibitor empagliflozin for 6 months. Obesity-induced VR cell depletion was also reversed by 3 months post-bariatric surgery. These findings collectively provided a mechanistic link between T2D, obesity, and impaired vessel homeostasis/repair, and also established that VRCE may be therapeutically reversed in a high CV-risk diabetic milieu.
FIERCE will assess VR cell content in individuals living with T2D (<10-years duration) and age- and sex-matched individuals not living with T2D. It will also assess the function of circulating ALDHhi VR cells through: (1) Endothelial peripheral arterial tonometry (EndoPAT) to clinically analyze endothelial function through reactive hyperemic index, (2) multipotent hematopoietic colony formation assays in vitro, (3) single-cell RNA-sequencing (scRNA-seq) that is focused on mRNA expression associated with angiogenesis, and (4) quantitative, label-free secretome analyses to determine changes in pro-angiogenic protein secretion.
The investigators hypothesize that VRCE impairs vascular repair and blood vessel regeneration during T2D and is partly caused by impaired pro-angiogenic properties of VR progenitor cell subsets. Specifically, the investigators postulate that multipotent hematopoietic colony formation, pro-angiogenic cytokine mRNA expression, and pro-angiogenic protein release will be lower in ALDHhi progenitor cell subsets from individuals living with T2D relative to participants not living with T2D. The investigators also predict that individuals living with T2D will exhibit a lower reactive hyperemic index compared to individuals not living with T2D.
Characterization of ALDHhi progenitor VR cell dysfunction in the setting of T2D will generate proof-of-concept to support the potential use of VR cell content as a quantifiable and functional indicator of vascular health.
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Type 2 Diabetes, Vascular regeneration, Hematopoietic progenitor cells, Functionality, EndoPAT, Endothelial dysfunction, scRNA-seq, Colony formation assay, Secretome analyses
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes | Participants living with type 2 diabetes for less than 10 years will be recruited. | |
| No Diabetes | Participants not living with diabetes will be recruited. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematopoietic colony formation in ALDHhiSSClow regenerative cell subsets
The capacity for total multipotent hematopoietic colony formation in ALDHhiSSClow regenerative cell subsets isolated from individuals living with T2D versus individuals not living with T2D.
Measured: Baseline
Secondary outcomes (2)
Endothelial function
Endothelial peripheral arterial tonometry (EndoPAT) will be utilized to clinically analyze endothelial function through reactive hyperemic index in individuals living with T2D and individuals not living with T2D.
Measured: Baseline
Frequency and absolute number of circulating ALDHhiSSClowCD133+ progenitor cells
The change in the frequency and absolute number of circulating ALDHhiSSClowCD133+ progenitor cells between individuals living with T2D versus age- and sex-matched individuals not living with T2D
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study startNov 2023 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Canadian Medical and Surgical Knowledge Translation Research Group
- Sponsor type
- University, hospital or other
- Collaborators
- Unity Health Toronto, University of Western Ontario, Canada
- Responsible party
- Sponsor
- Investigators
- Subodh Verma, MD, PhD, Principal investigator, Unity Health TorontoDavid A Hess, PhD, Principal investigator, Robarts Research Institute, London, Ontario
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06108388
- Sponsor's protocol ID
- Pro00074548
- Acronym
- FIERCE
- Status last verified
- Nov 2023
- First submitted
- 25 Oct 2023
- Last updated
- 13 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rawshani A, Rawshani A, Franzen S, Sattar N, Eliasson B, Svensson AM, Zethelius B, Miftaraj M, McGuire DK, Rosengren A, Gudbjornsdottir S. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2018 Aug 16;379(7):633-644. doi: 10.1056/NEJMoa1800256.
PubMed 30110583Haas AV, McDonnell ME. Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinol Metab Clin North Am. 2018 Mar;47(1):51-63. doi: 10.1016/j.ecl.2017.10.010.
PubMed 29407056Hess DA, Verma S, Bhatt D, Bakbak E, Terenzi DC, Puar P, Cosentino F. Vascular repair and regeneration in cardiometabolic diseases. Eur Heart J. 2022 Feb 10;43(6):450-459. doi: 10.1093/eurheartj/ehab758.
PubMed 34849704Szmitko PE, Fedak PW, Weisel RD, Stewart DJ, Kutryk MJ, Verma S. Endothelial progenitor cells: new hope for a broken heart. Circulation. 2003 Jun 24;107(24):3093-100. doi: 10.1161/01.CIR.0000074242.66719.4A. No abstract available.
PubMed 12821589Dimmeler S. Regulation of bone marrow-derived vascular progenitor cell mobilization and maintenance. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1088-93. doi: 10.1161/ATVBAHA.109.191668. Epub 2010 May 7.
PubMed 20453167Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005 May 3;45(9):1449-57. doi: 10.1016/j.jacc.2004.11.067.
PubMed 15862417Fadini GP, Boscaro E, de Kreutzenberg S, Agostini C, Seeger F, Dimmeler S, Zeiher A, Tiengo A, Avogaro A. Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes. Diabetes Care. 2010 May;33(5):1097-102. doi: 10.2337/dc09-1999. Epub 2010 Feb 11.
PubMed 20150295Mauch P, Hellman S. Loss of hematopoietic stem cell self-renewal after bone marrow transplantation. Blood. 1989 Aug 1;74(2):872-5.
PubMed 2665859Bigarella CL, Liang R, Ghaffari S. Stem cells and the impact of ROS signaling. Development. 2014 Nov;141(22):4206-18. doi: 10.1242/dev.107086.
PubMed 25371358Moore MA. Does stem cell exhaustion result from combining hematopoietic growth factors with chemotherapy? If so, how do we prevent it? Blood. 1992 Jul 1;80(1):3-7. No abstract available.
PubMed 1377052Mangialardi G, Spinetti G, Reni C, Madeddu P. Reactive oxygen species adversely impacts bone marrow microenvironment in diabetes. Antioxid Redox Signal. 2014 Oct 10;21(11):1620-33. doi: 10.1089/ars.2014.5944.
PubMed 25089632Terenzi 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.
PubMed 31053416Hayden J, O'Donnell G, deLaunois I, O'Gorman C. Endothelial Peripheral Arterial Tonometry (Endo-PAT 2000) use in paediatric patients: a systematic review. BMJ Open. 2023 Jan 18;13(1):e062098. doi: 10.1136/bmjopen-2022-062098.
PubMed 36657756Li Q, Wang M, Zhang S, Jin M, Chen R, Luo Y, Sun X. Single-cell RNA sequencing in atherosclerosis: Mechanism and precision medicine. Front Pharmacol. 2022 Oct 4;13:977490. doi: 10.3389/fphar.2022.977490. eCollection 2022.
PubMed 36267275Kehl D, Generali M, Mallone A, Heller M, Uldry AC, Cheng P, Gantenbein B, Hoerstrup SP, Weber B. Proteomic analysis of human mesenchymal stromal cell secretomes: a systematic comparison of the angiogenic potential. NPJ Regen Med. 2019 Apr 16;4:8. doi: 10.1038/s41536-019-0070-y. eCollection 2019.
PubMed 31016031
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Investigation of Endothelial Function and Regenerative Cell Exhaustion in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06108388
- Acronym / sponsor ID
- FIERCE / Pro00074548
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Type 2 Diabetes, Vascular regeneration, Hematopoietic progenitor cells, Functionality, EndoPAT, Endothelial dysfunction, scRNA-seq, Colony formation assay
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Canadian Medical and Surgical Knowledge Translation Research GroupUniversity, hospital or other
- Collaborators
- Unity Health Toronto, University of Western Ontario, Canada
- Study start
- Nov 2023 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 31 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
FIERCE is an observational cross-sectional study. Approximately 90 individuals living with type 2 diabetes (T2D) and/or individuals living without diabetes will be randomized (2:1).
The primary objective of this trial is to determine if there are differences in the content and function of circulating vascular regenerative (VR) progenitor cell subsets isolated from individuals living with T2D versus individuals not living with T2D. The main question this study aims to answer is: Does T2D compromise or enhance VR cell functionality?
Each participant will be asked to provide a single blood sample. Blood samples will be processed to enumerate the number of vessel-repairing cells and determine the functionality of the different subtypes of vessel-repairing cells.
Detailed description
Type 2 diabetes (T2D) is a significant and prevalent global health concern. Individuals diagnosed with T2D are at an elevated risk of developing atherosclerotic cardiovascular (CV) disease, a leading cause of global morbidity and mortality.
Blood vessel homeostasis plays a central role in the status of CV health. Circulating vascular regenerative (VR) progenitor cells, which mediate the endogenous processes of angiogenesis, vasculogenesis, and arteriogenesis, are critical in orchestrating vessel repair. In T2D, chronic hyperglycemia and concomitant oxidative stress create a maladaptive environment that impairs vessel repair. T2D can lead to a chronic state known as vascular regenerative cell exhaustion (VRCE), characterized by the depletion of, and dysfunction in, circulating VR progenitor cells. The available data indicate that VRCE associated with T2D can lead to VR cell dysfunction and compromised vascular repair.
The investigators have developed a multi-parametric flow cytometry assay to measure VR progenitor cell content in blood samples. This assay utilizes the cytosolic detoxification enzyme aldehyde dehydrogenase (ALDH), which is highly expressed in progenitor cells from hematopoietic, endothelial, and mesenchymal stromal cell lineages. This enzyme protects progenitor cells from oxidative damage that is driven by reactive oxygen species. ALDH activity is reduced by up to 100-fold as progenitor cells differentiate towards more expendable effector cells. As such, the investigators identify cells with high or low ALDH activity in combination with cell surface markers to distinguish progenitor cell subsets (ALDHhi) from more differentiated progeny (ALDHlow). Used in conjunction with 'side scatter' (SSC), a parameter that correlates with the granularity or complexity of a cell, this assay can distinguish between and quantify ALDHhiSSClow hematopoietic/endothelial precursor cells, ALDHhiSSCmid monocytes, and ALDHhiSSChi granulocyte precursors. Previously, bone marrow-derived ALDHhiSSClow cells were shown to co-express the primitive cell markers CD34 and CD133 and exhibit multipotent hematopoietic colony-forming ability in vitro. In the immunodeficient NOD/SCID mouse model of hindlimb ischemia, transplantation of ALDHhiSSClow cells into the ischemic limb led to improved muscle perfusion recovery. The potential of this cell therapy to prevent amputations in individuals with critical limb ischemia has been evaluated in clinical trial settings.
The peripheral blood of individuals living with T2D for >10-years exhibits a depletion of ALDHhiSSClow VR progenitor cells, lower frequencies of ALDHhiSSCmid monocytes with vessel reparative function, and an increased frequency of ALDHhiSSChi inflammatory granulocyte precursors compared to that from individuals not living with T2D. The VRCE phenotype was partially reversed in people living with T2D and established coronary artery disease (CAD) after they had been on the SGLT2 inhibitor empagliflozin for 6 months. Obesity-induced VR cell depletion was also reversed by 3 months post-bariatric surgery. These findings collectively provided a mechanistic link between T2D, obesity, and impaired vessel homeostasis/repair, and also established that VRCE may be therapeutically reversed in a high CV-risk diabetic milieu.
FIERCE will assess VR cell content in individuals living with T2D (<10-years duration) and age- and sex-matched individuals not living with T2D. It will also assess the function of circulating ALDHhi VR cells through: (1) Endothelial peripheral arterial tonometry (EndoPAT) to clinically analyze endothelial function through reactive hyperemic index, (2) multipotent hematopoietic colony formation assays in vitro, (3) single-cell RNA-sequencing (scRNA-seq) that is focused on mRNA expression associated with angiogenesis, and (4) quantitative, label-free secretome analyses to determine changes in pro-angiogenic protein secretion.
The investigators hypothesize that VRCE impairs vascular repair and blood vessel regeneration during T2D and is partly caused by impaired pro-angiogenic properties of VR progenitor cell subsets. Specifically, the investigators postulate that multipotent hematopoietic colony formation, pro-angiogenic cytokine mRNA expression, and pro-angiogenic protein release will be lower in ALDHhi progenitor cell subsets from individuals living with T2D relative to participants not living with T2D. The investigators also predict that individuals living with T2D will exhibit a lower reactive hyperemic index compared to individuals not living with T2D.
Characterization of ALDHhi progenitor VR cell dysfunction in the setting of T2D will generate proof-of-concept to support the potential use of VR cell content as a quantifiable and functional indicator of vascular health.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetes | – | –Participants living with type 2 diabetes for less than 10 years will be recruited. |
| No Diabetes | – | –Participants not living with diabetes will be recruited. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be identified from primary care clinics in the Greater Toronto Area using paper-based and electronic medical records.
Key inclusion criteria (4 listed)
- Adults ≥18 years of age.
- Willing to provide written informed consent.
- Documented history of T2D
- No documented history of diabetes
Key exclusion criteria (9 listed)
- Unable or unwilling to provide written informed consent or provide a peripheral blood sample.
- Any life-threatening disease expected to result in death within two years of consent.
- Any malignancy not considered cured (except basal cell carcinoma of the skin). An individual is considered cured if there has been no evidence of cancer recurrence for the five years prior to screening.
- Known severe liver disease.
- White blood cell count ≥15 x 10^9/L.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hematopoietic colony formation in ALDHhiSSClow regenerative cell subsets
Time frame: Baseline
The capacity for total multipotent hematopoietic colony formation in ALDHhiSSClow regenerative cell subsets isolated from individuals living with T2D versus individuals not living with T2D.
2 secondary outcomes
Endothelial function
Time frame: Baseline
Frequency and absolute number of circulating ALDHhiSSClowCD133+ progenitor cells
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2023.
- Background: PubMed 30110583Rawshani A, Rawshani A, Franzen S, Sattar N, Eliasson B, Svensson AM, Zethelius B, Miftaraj M, McGuire DK, Rosengren A, Gudbjornsdottir S. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2018 Aug 16;379(7):633-644. doi: 10.1056/NEJMoa1800256.
- Background: PubMed 29407056Haas AV, McDonnell ME. Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinol Metab Clin North Am. 2018 Mar;47(1):51-63. doi: 10.1016/j.ecl.2017.10.010.
- Background: PubMed 34849704Hess DA, Verma S, Bhatt D, Bakbak E, Terenzi DC, Puar P, Cosentino F. Vascular repair and regeneration in cardiometabolic diseases. Eur Heart J. 2022 Feb 10;43(6):450-459. doi: 10.1093/eurheartj/ehab758.
- Background: PubMed 12821589Szmitko PE, Fedak PW, Weisel RD, Stewart DJ, Kutryk MJ, Verma S. Endothelial progenitor cells: new hope for a broken heart. Circulation. 2003 Jun 24;107(24):3093-100. doi: 10.1161/01.CIR.0000074242.66719.4A. No abstract available.
- Background: PubMed 20453167Dimmeler S. Regulation of bone marrow-derived vascular progenitor cell mobilization and maintenance. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1088-93. doi: 10.1161/ATVBAHA.109.191668. Epub 2010 May 7.
- Background: PubMed 15862417Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005 May 3;45(9):1449-57. doi: 10.1016/j.jacc.2004.11.067.
- Background: PubMed 20150295Fadini GP, Boscaro E, de Kreutzenberg S, Agostini C, Seeger F, Dimmeler S, Zeiher A, Tiengo A, Avogaro A. Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes. Diabetes Care. 2010 May;33(5):1097-102. doi: 10.2337/dc09-1999. Epub 2010 Feb 11.
- Background: PubMed 2665859Mauch P, Hellman S. Loss of hematopoietic stem cell self-renewal after bone marrow transplantation. Blood. 1989 Aug 1;74(2):872-5.
- Background: PubMed 25371358Bigarella CL, Liang R, Ghaffari S. Stem cells and the impact of ROS signaling. Development. 2014 Nov;141(22):4206-18. doi: 10.1242/dev.107086.
- Background: PubMed 1377052Moore MA. Does stem cell exhaustion result from combining hematopoietic growth factors with chemotherapy? If so, how do we prevent it? Blood. 1992 Jul 1;80(1):3-7. No abstract available.
- Background: PubMed 25089632Mangialardi G, Spinetti G, Reni C, Madeddu P. Reactive oxygen species adversely impacts bone marrow microenvironment in diabetes. Antioxid Redox Signal. 2014 Oct 10;21(11):1620-33. doi: 10.1089/ars.2014.5944.
- Background: PubMed 31053416Terenzi 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.
- IDF Diabetes atlas, 10th ed.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Subodh Verma, MD, PhD principal investigator
Unity Health Toronto
David A Hess, PhD principal investigator
Robarts Research Institute, London, Ontario
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2, run by Canadian Medical and Surgical Knowledge Translation Research Group at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fallon Dennis, BMSc (7057720021, fallon.dennis@mail.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hematopoietic colony formation in ALDHhiSSClow regenerative cell subsets (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06108388, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2023; AzTrials last refreshed its copy on 6 Nov 2026.