Semaglutide and Vascular Regeneration

NCT05870462 | Unknown Phase 4

• 1 other identifier: Pro00068765
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Obesity

Keywords

GLP-1 receptor agonists; GLP-1; Semaglutide; Vascular regeneration; Inflammation; Monocytes; Granulocytes; Hematopoietic progenitor cells; Cardiovascular risk; Type 2 diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Changes in the mean frequency (%) of circulating ALDHhiSSClow primitive progenitor cells in individuals treated with semaglutide versus usual care for 6 months

  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

  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

  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

  Baseline to 6 months post-randomization

Study Arms (2)

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.

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.

Interventions

Semaglutide Pen Injector DRUG

* 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.

Also known as: Ozempic, Wegovy

Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Canadian Medical and Surgical Knowledge Translation Research Group: lead
• Unity Health Toronto: collaborator
• Western University, Canada: collaborator

Study Sites (2)

North York Diagnostic and Cardiac Centre

North York, Ontario, M6B 1N6, Canada

RECRUITING

Diagnostic Assessment Centre

Scarborough Village, Ontario, M1S4N6, Canada

RECRUITING

Related Publications (11)

• 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.

  PMID: 34849704 BACKGROUND

• 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.

  PMID: 33554145 BACKGROUND

• Ghattas 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.

  PMID: 23973684 BACKGROUND

• Drucker 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.

  PMID: 17098089 BACKGROUND

• Cappellari 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.

  PMID: 32306097 RESULT

• Terenzi 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.

  PMID: 30847424 RESULT

• Hess 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.

  PMID: 31477497 RESULT

• Hess 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.

  PMID: 33205058 RESULT

• Sorli 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.

  PMID: 28110911 RESULT

• Marso 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.

  PMID: 27633186 RESULT

• Sattar 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.

  PMID: 34425083 RESULT

MeSH Terms

Conditions

Atherosclerosis; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Obesity; Inflammation

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Subodh Verma, MD, PhD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• David A Hess, PhD

  Robarts Research Institute, London, Ontario

  PRINCIPAL INVESTIGATOR

• David Mazer, MD

  Unity Health Toronto

  STUDY CHAIR

• Hwee Teoh, PhD

  Unity Health Toronto

  STUDY CHAIR

Central Study Contacts

Brady Park, BMSc

CONTACT

2262359725; brady.park@mail.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 23, 2023
• Study Start: April 29, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)