AtherosclerosisPhase 4SEMA-VRNCT05870462
Semaglutide and Vascular Regeneration
A Phase 4 study testing Semaglutide Pen Injector in people with Atherosclerosis and Cardiovascular Diseases, run by Canadian Medical and Surgical Knowledge Translation Research Group at 2 sites in Canada.
Trial summary
SEMA-VR is a prospective, randomized, 6-month long, open-label study of semaglutide. Approximately 100 participants with type 2 diabetes and/or obesity will be randomized (1:1) to receive semaglutide at escalating doses (up to 1.0 mg/week) or usual care without semaglutide for 6 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atherosclerosis, Cardiovascular Diseases, Diabetes Mellitus, Type 2
- What is being tested?
- Semaglutide Pen Injector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesCanada
- Study dates
- 29 Apr 2023to Dec 2024
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 18 years of age who meet one of the following Health Canada indications to receive subcutaneous semaglutide injections:
- Documented T2D with inadequate glycemic control
- Body mass index (BMI) ≥ 30 kg/m^2 (obesity)
- BMI ≥ 27 kg/m^2 (overweight) and at least one weight-related comorbidity, such as hypertension, dyslipidemia, or obstructive sleep apnea
- AND meet one of the following ASCVD criteria:
- History of ASCVD:
Show all 20Show fewer
- Documented coronary artery disease
- Documented cerebrovascular or carotid disease
- Documented peripheral artery disease
- No ASCVD but has 2 or more of the following risk factors:
- Cigarette smoker or stopped smoking within 3 months of screening
- Persistent hypertension (defined as office blood pressure ≥ 140/90 mmHg) or currently on antihypertensive medications
- BMI ≥ 27 kg/m^2
- estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m^2
- Treated or untreated dyslipidemia
- Triglyceride ≥ 2.0 mmol/L
- HDL-C ≤ 1.0 mmol/L for men or ≤ 1.3 mmol/L for women
- High sensitivity C-reactive protein (hsCRP) ≥ 2.0 mg/L
- Documented micro- or macro-albuminuria
- Self-identified South Asian ethnicity
Who cannot join
- Female subjects who are pregnant, planning pregnancy, or breastfeeding
- HbA1c > 11.0 %
- Currently on a GLP-1RA or previously taken a GLP-1RA
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- New York Heart Association class IV symptoms of heart failure
Show all 13Show fewer
- Known history of severe liver disease (e.g. Child-Pugh Class B or C)
- White blood cell count ≥ 15 x 10^9/L
- Active infectious disease requiring antibiotic or anti-viral agents
- Known acquired immunodeficiency syndrome such as HIV
- On oral steroid therapy (e.g. prednisone or other corticosteroids) or other immunosuppressive agents (e.g. methotrexate)
- 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
- Any clinically significant or unstable medical condition that might limit one's ability to complete the study or comply with the requirements of the protocol, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease, and psychiatric disease
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
North York Diagnostic and Cardiac Centre
North York, Ontario, M6B 1N6
Subodh Verma, MD, PhD
- Recruiting
Diagnostic Assessment Centre
Scarborough Village, Ontario, M1S4N6
Subodh Verma, MD, PhD
About this study
Official title: Semaglutide and Vascular Regeneration in People With Diabetes and/or Obesity
SEMA-VR is a prospective, randomized, 6-month long, open-label study of semaglutide. Approximately 100 participants with type 2 diabetes and/or obesity will be randomized (1:1) to receive semaglutide at escalating doses (up to 1.0 mg/week) or usual care without semaglutide for 6 months.
The goal of this trial is to understand how semaglutide exerts cardio-protective effects in people with type 2 diabetes and/or obesity. The main question it aims to answer is:
Read more
- Does semaglutide treatment preserve or increase the number of vessel-repairing cells circulating in the blood?
Participants will:
- Be allocated to receive either semaglutide or usual care for 6 months
- Provide a blood sample at the baseline visit and another blood sample at the 6-month visit
Researchers will compare participants receiving semaglutide to those receiving usual care for any differences in the 6-month change in the number of vessel-repairing cells in the blood.
Read the detailed description
The leading cause of death in people with type 2 diabetes (T2D) and/or obesity is atherosclerotic cardiovascular disease (ASCVD). Arterial damage and repair are regulated by mechanisms of vessel homeostasis, which include vasculogenesis (de novo blood vessel synthesis), angiogenesis (vessel formation from pre-existing vessels), and arteriogenesis (re-modelling of collateral vessels). Key cellular modulators of these processes include hematopoietic stem/progenitor cells (HPC) and their myeloid progenies, together referred to as vascular regenerative cells.
An established and innovative multi-parametric flow cytometry assay that utilizes lineage-specific cell surface marker expression and aldehyde dehydrogenase (ALDH) activity will be used to characterize and quantify vascular regenerative cells from peripheral blood samples. Using this assay, three distinct populations of vascular regenerative cells within the hematopoietic hierarchy have been previously identified:
- ALDHhiSSClow (high ALDH activity, low side scatter/granular complexity) represent primitive progenitor cells, such as HPCs, that secrete chemo-attractant cytokines to recruit other circulating vascular regenerative cells to sites of vessel damage and ischemia.
- ALDHhiSSCmid cells represent macrophage precursor cells (i.e. monocytes) classified along a spectrum of pro-inflammatory subtypes versus pro-vascular subtypes that remodel arterial occlusions.
- ALDHhiSSChi cells represent granulocyte precursors, consisting of a heterogeneous group of pro-inflammatory subtypes that aggravate atherosclerosis and endothelial damage, along with pro-angiogenic subtypes that reduce inflammation and support vessel repair.
Using this multi-parametric flow cytometry assay, it has been previously reported that people with T2D presented lower frequencies of vascular regenerative cells in their peripheral blood compared to people without T2D. In addition, these frequencies were increased in response to the antihyperglycemic agent empagliflozin and bariatric surgery, suggesting that this regenerative cell deficiency can be reversed. Specifically, three months after bariatric surgery, frequencies of ALDHhiSSClow primitive progenitor cells and pro-vascular ALDHhiSSCmid monocytes in the peripheral blood were increased, whereas frequencies of pro-inflammatory monocytes and ALDHhiSSChi granulocyte precursors were decreased. These studies established circulating vascular regenerative cells as key mechanistic constituents of vessel homeostasis that can be quantified from readily available blood samples, and highlighted the utility of the multi-parametric flow cytometry assay in providing high-throughput, real-time biological readouts of vascular repair potential or deficiency.
Semaglutide belongs to a drug class known as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA). Semaglutide mimics the actions of GLP-1, a gut hormone that is released after a meal and triggers a range of metabotropic effects such as elevating insulin release, reducing food motility, and increasing satiety. In landmark clinical trials, weekly semaglutide injections led to a 1.9% reduction in HbA1c, 16% weight loss in adults and teens, and a 26% reduction in major ASCVD events.
The precise mechanism(s) underlying the effect of semaglutide on ASCVD reduction remain poorly defined. In light of previous observations (described above), the investigators hypothesize that in people with T2D, semaglutide add-on to usual care will be superior to usual care alone in the restoration of vascular regenerative cell frequency. Specifically, the investigators predict significantly greater baseline to 6 month increases in the frequency of ALDHhiSSClow primitive progenitor cells and pro-vascular ALDHhiSSCmid monocytes, along with decreases in pro-inflammatory monocytes and ALDHhiSSChi granulocyte precursors in the semaglutide-assigned group compared to the usual care group.
Findings from this study will reveal whether semaglutide affects the quantity of circulating vascular regenerative cells responsible for vessel repair, thereby providing a potential mechanism of action behind the reduction of ASCVD events observed in GLP-1RA cardiovascular outcome trials.
- Being tested
- Semaglutide Pen Injector
- Keywords
- GLP-1 receptor agonists, GLP-1, Semaglutide, Vascular regeneration, Inflammation, Monocytes, Granulocytes, Hematopoietic progenitor cells, Cardiovascular risk, Type 2 diabetes, Obesity
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Obesity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Pen InjectorDrug
Also called Ozempic, Wegovy
- 0.25 mg/week (non-therapeutic dose) during Weeks 1-4
- 0.50 mg/week during Weeks 5-8
- 1.0 mg/week during Weeks 9-24
Participants experiencing side effects (e.g. nausea, stomach pain, constipation, diarrhea, vomiting) at the maximum dose (1.0 mg/week) may be down-titrated to 0.50 mg/week.
Participants who had been receiving a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin, saxagliptin, linagliptin, alogliptin) will stop taking their DPP-4 inhibitor upon randomization to this arm.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Participants will receive once-weekly semaglutide subcutaneous injection [Ozempic] at escalating doses from 0.25 mg/week, 0.5 mg/week, to 1.0 mg/week. Receives: Drug: Semaglutide Pen Injector |
| Usual care | No intervention | Participants will continue to receive other usual medications, rehabilitation, procedures, and interventions as recommended by their healthcare providers. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the mean frequency (%) of circulating ALDHhiSSClow primitive progenitor cells in individuals treated with semaglutide versus usual care for 6 months
Measured: Baseline to 6 months post-randomization
Secondary outcomes (3)
Changes in the mean frequency (%) of circulating ALDHhiSSCmid pro-vascular monocytes in individuals treated with semaglutide versus usual care for 6 months
Measured: Baseline to 6 months post-randomization
Changes in the frequency (%) of circulating ALDHhiSSCmid pro-inflammatory monocytes in individuals treated with semaglutide versus usual care for 6 months
Measured: Baseline to 6 months post-randomization
Changes in the frequency (%) of circulating ALDHhiSSChi pro-inflammatory granulocyte precursors in individuals treated with semaglutide versus usual care for 6 months
Measured: Baseline to 6 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start29 Apr 2023
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 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, Western University, Canada
- Responsible party
- Sponsor
- Investigators
- Subodh Verma, MD, PhD, Principal investigator, Unity Health TorontoDavid A Hess, PhD, Principal investigator, Robarts Research Institute, London, OntarioDavid Mazer, MD, Study chair, Unity Health TorontoHwee Teoh, PhD, Study chair, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05870462
- Sponsor's protocol ID
- Pro00068765
- Acronym
- SEMA-VR
- Status last verified
- Jul 2023
- First submitted
- 28 Apr 2023
- Last updated
- 25 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hess 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 34849704Terenzi 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.
PubMed 33554145Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013 Oct 22;62(17):1541-51. doi: 10.1016/j.jacc.2013.07.043. Epub 2013 Aug 21.
PubMed 23973684Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.
PubMed 17098089Cappellari R, D'Anna M, Menegazzo L, Bonora BM, Albiero M, Avogaro A, Fadini GP. Diabetes mellitus impairs circulating proangiogenic granulocytes. Diabetologia. 2020 Sep;63(9):1872-1884. doi: 10.1007/s00125-020-05142-3. Epub 2020 Apr 18.
PubMed 32306097Terenzi DC, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes. JACC Basic Transl Sci. 2018 Nov 5;4(1):98-112. doi: 10.1016/j.jacbts.2018.10.005. eCollection 2019 Feb.
PubMed 30847424Hess DA, Terenzi DC, Trac JZ, Quan A, Mason T, Al-Omran M, Bhatt DL, Dhingra N, Rotstein OD, Leiter LA, Zinman B, Sabongui S, Yan AT, Teoh H, Mazer CD, Connelly KA, Verma S. SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus. Cell Metab. 2019 Oct 1;30(4):609-613. doi: 10.1016/j.cmet.2019.08.015. Epub 2019 Aug 30.
PubMed 31477497Hess DA, Trac JZ, Glazer SA, Terenzi DC, Quan A, Teoh H, Al-Omran M, Bhatt DL, Mazer CD, Rotstein OD, Verma S. Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery. Cell Rep Med. 2020 May 19;1(2):100018. doi: 10.1016/j.xcrm.2020.100018. eCollection 2020 May 19.
PubMed 33205058Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbol JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017 Apr;5(4):251-260. doi: 10.1016/S2213-8587(17)30013-X. Epub 2017 Jan 17.
PubMed 28110911Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
PubMed 27633186Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, Lam CSP, Lopes RD, McMurray JJV, Pratley RE, Rosenstock J, Gerstein HC. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021 Oct;9(10):653-662. doi: 10.1016/S2213-8587(21)00203-5. Epub 2021 Aug 20.
PubMed 34425083
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Semaglutide and Vascular Regeneration in People With Diabetes and/or Obesity
- ClinicalTrials.gov ID
- NCT05870462
- Acronym / sponsor ID
- SEMA-VR / Pro00068765
- Keywords
- GLP-1 receptor agonists, GLP-1, Semaglutide, Vascular regeneration, Inflammation, Monocytes, Granulocytes, Hematopoietic progenitor cells
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Canadian Medical and Surgical Knowledge Translation Research GroupUniversity, hospital or other
- Collaborators
- Unity Health Toronto, Western University, Canada
- Study start
- 29 Apr 2023 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 23 May 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.
SEMA-VR is a prospective, randomized, 6-month long, open-label study of semaglutide. Approximately 100 participants with type 2 diabetes and/or obesity will be randomized (1:1) to receive semaglutide at escalating doses (up to 1.0 mg/week) or usual care without semaglutide for 6 months.
The goal of this trial is to understand how semaglutide exerts cardio-protective effects in people with type 2 diabetes and/or obesity. The main question it aims to answer is:
- Does semaglutide treatment preserve or increase the number of vessel-repairing cells circulating in the blood?
Participants will:
- Be allocated to receive either semaglutide or usual care for 6 months
- Provide a blood sample at the baseline visit and another blood sample at the 6-month visit
Researchers will compare participants receiving semaglutide to those receiving usual care for any differences in the 6-month change in the number of vessel-repairing cells in the blood.
Detailed description
The leading cause of death in people with type 2 diabetes (T2D) and/or obesity is atherosclerotic cardiovascular disease (ASCVD). Arterial damage and repair are regulated by mechanisms of vessel homeostasis, which include vasculogenesis (de novo blood vessel synthesis), angiogenesis (vessel formation from pre-existing vessels), and arteriogenesis (re-modelling of collateral vessels). Key cellular modulators of these processes include hematopoietic stem/progenitor cells (HPC) and their myeloid progenies, together referred to as vascular regenerative cells.
An established and innovative multi-parametric flow cytometry assay that utilizes lineage-specific cell surface marker expression and aldehyde dehydrogenase (ALDH) activity will be used to characterize and quantify vascular regenerative cells from peripheral blood samples. Using this assay, three distinct populations of vascular regenerative cells within the hematopoietic hierarchy have been previously identified:
- ALDHhiSSClow (high ALDH activity, low side scatter/granular complexity) represent primitive progenitor cells, such as HPCs, that secrete chemo-attractant cytokines to recruit other circulating vascular regenerative cells to sites of vessel damage and ischemia.
- ALDHhiSSCmid cells represent macrophage precursor cells (i.e. monocytes) classified along a spectrum of pro-inflammatory subtypes versus pro-vascular subtypes that remodel arterial occlusions.
- ALDHhiSSChi cells represent granulocyte precursors, consisting of a heterogeneous group of pro-inflammatory subtypes that aggravate atherosclerosis and endothelial damage, along with pro-angiogenic subtypes that reduce inflammation and support vessel repair.
Using this multi-parametric flow cytometry assay, it has been previously reported that people with T2D presented lower frequencies of vascular regenerative cells in their peripheral blood compared to people without T2D. In addition, these frequencies were increased in response to the antihyperglycemic agent empagliflozin and bariatric surgery, suggesting that this regenerative cell deficiency can be reversed. Specifically, three months after bariatric surgery, frequencies of ALDHhiSSClow primitive progenitor cells and pro-vascular ALDHhiSSCmid monocytes in the peripheral blood were increased, whereas frequencies of pro-inflammatory monocytes and ALDHhiSSChi granulocyte precursors were decreased. These studies established circulating vascular regenerative cells as key mechanistic constituents of vessel homeostasis that can be quantified from readily available blood samples, and highlighted the utility of the multi-parametric flow cytometry assay in providing high-throughput, real-time biological readouts of vascular repair potential or deficiency.
Semaglutide belongs to a drug class known as glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA). Semaglutide mimics the actions of GLP-1, a gut hormone that is released after a meal and triggers a range of metabotropic effects such as elevating insulin release, reducing food motility, and increasing satiety. In landmark clinical trials, weekly semaglutide injections led to a 1.9% reduction in HbA1c, 16% weight loss in adults and teens, and a 26% reduction in major ASCVD events.
The precise mechanism(s) underlying the effect of semaglutide on ASCVD reduction remain poorly defined. In light of previous observations (described above), the investigators hypothesize that in people with T2D, semaglutide add-on to usual care will be superior to usual care alone in the restoration of vascular regenerative cell frequency. Specifically, the investigators predict significantly greater baseline to 6 month increases in the frequency of ALDHhiSSClow primitive progenitor cells and pro-vascular ALDHhiSSCmid monocytes, along with decreases in pro-inflammatory monocytes and ALDHhiSSChi granulocyte precursors in the semaglutide-assigned group compared to the usual care group.
Findings from this study will reveal whether semaglutide affects the quantity of circulating vascular regenerative cells responsible for vessel repair, thereby providing a potential mechanism of action behind the reduction of ASCVD events observed in GLP-1RA cardiovascular outcome trials.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: Semaglutide Pen InjectorParticipants will receive once-weekly semaglutide subcutaneous injection [Ozempic] at escalating doses from 0.25 mg/week, 0.5 mg/week, to 1.0 mg/week. |
| Usual care | No intervention | –Participants will continue to receive other usual medications, rehabilitation, procedures, and interventions as recommended by their healthcare providers. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Adults ≥ 18 years of age who meet one of the following Health Canada indications to receive subcutaneous semaglutide injections:
- AND meet one of the following ASCVD criteria:
Key exclusion criteria (13 listed)
- Female subjects who are pregnant, planning pregnancy, or breastfeeding
- HbA1c > 11.0 %
- Currently on a GLP-1RA or previously taken a GLP-1RA
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide Pen InjectorAlso: Ozempic, Wegovy* 0.25 mg/week (non-therapeutic dose) during Weeks 1-4 * 0.50 mg/week during Weeks 5-8 * 1.0 mg/week during Weeks 9-24 Participants experiencing side effects (e.g. nausea, stomach pain, constipation, diarrhea, vomiting) at the maximum dose (1.0 mg/week) may be down-titrated to 0.50 mg/week. Participants who had been receiving a dipeptidyl peptidase 4 (DPP-4) inhibitor (sitagliptin, saxagliptin, linagliptin, alogliptin) will stop taking their DPP-4 inhibitor upon randomization to this arm. | Drug | Semaglutide |
Primary outcome
Changes in the mean frequency (%) of circulating ALDHhiSSClow primitive progenitor cells in individuals treated with semaglutide versus usual care for 6 months
Time frame: Baseline to 6 months post-randomization
3 secondary outcomes
Changes in the mean frequency (%) of circulating ALDHhiSSCmid pro-vascular monocytes in individuals treated with semaglutide versus usual care for 6 months
Time frame: Baseline to 6 months post-randomization
Changes in the frequency (%) of circulating ALDHhiSSCmid pro-inflammatory monocytes in individuals treated with semaglutide versus usual care for 6 months
Time frame: Baseline to 6 months post-randomization
Changes in the frequency (%) of circulating ALDHhiSSChi pro-inflammatory granulocyte precursors in individuals treated with semaglutide versus usual care for 6 months
Time frame: Baseline to 6 months post-randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- 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 33554145Terenzi 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.
- Background: PubMed 23973684Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013 Oct 22;62(17):1541-51. doi: 10.1016/j.jacc.2013.07.043. Epub 2013 Aug 21.
- Background: PubMed 17098089Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006 Nov 11;368(9548):1696-705. doi: 10.1016/S0140-6736(06)69705-5.
- Results publication: PubMed 32306097Cappellari R, D'Anna M, Menegazzo L, Bonora BM, Albiero M, Avogaro A, Fadini GP. Diabetes mellitus impairs circulating proangiogenic granulocytes. Diabetologia. 2020 Sep;63(9):1872-1884. doi: 10.1007/s00125-020-05142-3. Epub 2020 Apr 18.
- Results publication: PubMed 30847424Terenzi DC, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes. JACC Basic Transl Sci. 2018 Nov 5;4(1):98-112. doi: 10.1016/j.jacbts.2018.10.005. eCollection 2019 Feb.
- Results publication: PubMed 31477497Hess DA, Terenzi DC, Trac JZ, Quan A, Mason T, Al-Omran M, Bhatt DL, Dhingra N, Rotstein OD, Leiter LA, Zinman B, Sabongui S, Yan AT, Teoh H, Mazer CD, Connelly KA, Verma S. SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus. Cell Metab. 2019 Oct 1;30(4):609-613. doi: 10.1016/j.cmet.2019.08.015. Epub 2019 Aug 30.
- Results publication: PubMed 33205058Hess DA, Trac JZ, Glazer SA, Terenzi DC, Quan A, Teoh H, Al-Omran M, Bhatt DL, Mazer CD, Rotstein OD, Verma S. Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content following Bariatric Surgery. Cell Rep Med. 2020 May 19;1(2):100018. doi: 10.1016/j.xcrm.2020.100018. eCollection 2020 May 19.
- Results publication: PubMed 28110911Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbol JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017 Apr;5(4):251-260. doi: 10.1016/S2213-8587(17)30013-X. Epub 2017 Jan 17.
- Results publication: PubMed 27633186Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsboll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15.
- Results publication: PubMed 34425083Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, Lam CSP, Lopes RD, McMurray JJV, Pratley RE, Rosenstock J, Gerstein HC. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021 Oct;9(10):653-662. doi: 10.1016/S2213-8587(21)00203-5. Epub 2021 Aug 20.
- Individual participant dataSharing planned: No
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Peripheral Artery Disease (PAD), Intermittent Claudication
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
Active, not recruiting
Thromboelastography With Platelet Mapping to Guide Antiplatelet Therapy After Lower Extremity Revascularization
Thrombosis, Arterial Occlusive Diseases
Enrolling by invitation
The DANE-HEART Trial - Computed Tomography Coronary Angiography for Primary Prevention
Coronary Atherosclerosis and Other Heart Disease, Cardiovascular Diseases
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
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
David Mazer, MD study chair
Unity Health Toronto
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide Pen Injector in people with Atherosclerosis and Cardiovascular Diseases, run by Canadian Medical and Surgical Knowledge Translation Research Group at 2 sites 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 20 inclusion and 13 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 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Brady Park, BMSc (2262359725, brady.park@mail.utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the mean frequency (%) of circulating ALDHhiSSClow primitive progenitor cells in individuals treated with semaglutide versus usual care for 6 months (time frame: Baseline to 6 months post-randomization). 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 NCT05870462, which also lists 11 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 25 Jul 2023.