Effect of Oral Semaglutide on Epicardial and Pericoronary Adipose Tissues in Type 2 Diabetes After Myocardial Infarction

NCT06557811 | Not Yet Recruiting Phase 4

• 1 other identifier: 75667623.1.0000.0068
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate the ability of oral semaglutide to reduce pericardial and perivascular fat as well as coronary plaque in type 2 diabetic patients after acute myocardial infarction. Patients of both sexes, aged 50 years or older, diagnosed with type 2 diabetes and with a previous acute myocardial infarction between more than 2 and less than 9 months ago, will be included. The primary objective is to investigate the ability of oral semaglutide to reduce pericardial and perivascular fat in type 2 diabetics after myocardial infarction. The primary outcome will be composed of three measures: Measurement of pericardial adipose tissue at 180 days; Measurement of the perivascular adipose tissue attenuation index at 180 days; Measurement of the fat attenuation index at 180 days. To assess the degree of epicardial and perivascular fat attenuation, coronary artery computed tomography will be performed, and to evaluate the left ventricular ejection fraction, transthoracic echocardiography will be conducted. Oral semaglutide may reduce pericardial and/or perivascular fat in diabetics after acute myocardial infarction.

Conditions

Diabetic Patients; Acute Myocardial Infarction

Keywords

Diabetes; Acute myocardial infarction; Oral Semaglutide

Outcome Measures

Primary Outcomes (3)

• Measurement of pericardial adipose tissue at 180 days

  Measurement of pericardial adipose tissue (cm³)

  180 days

• Measurement of the fat attenuation index at 180 days

  Measurement of the fat attenuation index (Hounsfield units (HU))

  180 days

• Measurement of the perivascular adipose tissue attenuation index at 180 days

  Measurement of the perivascular adipose tissue attenuation index (Hounsfield units (HU))

  180 days

Secondary Outcomes (23)

• Determination of metabolic marker levels fasting blood glucose

  180 days

• Determination of metabolic marker levels HbA1c

  180 days

• Determination of metabolic marker levels Insulin

  180 days

• Determination of metabolic marker levels HOMA-IR

  180 days

• Determination of metabolic marker levels total cholesterol and fractions

  180 days

Study Arms (2)

Semaglutide

OTHER

2 groups: This group will receive semaglutide

Drug: Semaglutide

Placebo

OTHER

2 groups: This group will receive placebo (control population).

Drug: Semaglutide

Interventions

Semaglutide DRUG

After randomization, each patient will receive four blisters of 3 mg tablets (semaglutide or placebo) and four blisters of 7 mg tablets (semaglutide or placebo), to be taken before breakfast. After 60 days, the patient will receive a 14 mg dose (a total of 16 blisters with 7 tablets each). The possibility of maintaining the 14 mg dose of the study drug or reducing it to 7 mg will be evaluated depending on side effects and tolerability.

Also known as: Rybelsus

Placebo; Semaglutide

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient aged 50 years or older at the time of screening, diagnosed with type 2 diabetes and with a previous acute myocardial infarction more than 2 and less than 9 months ago, with the following conditions:
• Signed Informed Consent Form.
• BMI ≥ 25 and \< 40 kg/m².
• The following glucose-lowering agents are permitted: any insulin, insulin analogs, sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and SGLT-2 inhibitors (iSGLT2).
• Patients using iSGLT2 will not be excluded because they receive this medication at no cost at InCor with benefits for the treatment of type 2 diabetes. Furthermore, there would be an impact on ethical issues and the control of this prescription in other clinics. Thus, we will list the patients using SGLT2 inhibitors and statistically evaluate the comparison with the group that did not use this medication.

You may not qualify if:

• Patients with type 1 diabetes.
• Type 2 diabetes currently or previously treated (within 90 days prior to screening) with any GLP-1RA and DPP-4 inhibitor.
• Those not properly treated for previously diagnosed hypothyroidism.
• Diagnosed with NYHA class IV heart failure.
• Myocardial infarction more than 9 months after diagnosis.
• Any of the following: myocardial infarction, stroke, or hospitalization for unstable angina or transient ischemic attack within 60 days before screening.
• Any contraindication present in the package insert for the use of GLP1-RA or Oral Semaglutide.
• Desire to become pregnant.
• Previous history of pancreatitis (acute or chronic).
• Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
• History of major surgical procedures involving the stomach, potentially affecting the absorption of the test product (e.g., subtotal and total gastrectomy, vertical gastrectomy, gastric bypass surgery).
• Planned and known coronary, carotid, or peripheral arterial revascularization on the day of screening.
• Chronic or intermittent hemodialysis, peritoneal dialysis, or severe renal insufficiency (corresponding to eGFR \< 30 mL/min/1.73 m²) - due to CT specifications reported below.
• History or presence of malignant neoplasm in the last 5 years (except basal cell and squamous cell skin cancer and carcinoma in situ).
• History of diabetic ketoacidosis.

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Study Sites (1)

ARO (Academic Research Organization)

São Paulo, São Paulo, 05403-900, Brazil

Location

Related Publications (22)

• Tsaban G, Wolak A, Avni-Hassid H, Gepner Y, Shelef I, Henkin Y, Schwarzfuchs D, Cohen N, Bril N, Rein M, Serfaty D, Kenigsbuch S, Tene L, Zelicha H, Yaskolka-Meir A, Komy O, Bilitzky A, Chassidim Y, Ceglarek U, Stumvoll M, Bluher M, Thiery J, Dicker D, Rudich A, Stampfer MJ, Shai I. Dynamics of intrapericardial and extrapericardial fat tissues during long-term, dietary-induced, moderate weight loss. Am J Clin Nutr. 2017 Oct;106(4):984-995. doi: 10.3945/ajcn.117.157115. Epub 2017 Aug 16.

  PMID: 28814394 BACKGROUND

• Iacobellis G. Epicardial adipose tissue in endocrine and metabolic diseases. Endocrine. 2014 May;46(1):8-15. doi: 10.1007/s12020-013-0099-4. Epub 2013 Nov 23.

  PMID: 24272604 BACKGROUND

• Lazaros G, Antonopoulos A, Antoniades C, Tousoulis D. The Role of Epicardial Fat in Pericardial Diseases. Curr Cardiol Rep. 2018 Apr 19;20(6):40. doi: 10.1007/s11886-018-0986-7.

  PMID: 29675684 BACKGROUND

• Russo R, Di Iorio B, Di Lullo L, Russo D. Epicardial adipose tissue: new parameter for cardiovascular risk assessment in high risk populations. J Nephrol. 2018 Dec;31(6):847-853. doi: 10.1007/s40620-018-0491-5. Epub 2018 Apr 27.

  PMID: 29704210 BACKGROUND

• Nagy E, Jermendy AL, Merkely B, Maurovich-Horvat P. Clinical importance of epicardial adipose tissue. Arch Med Sci. 2017 Jun;13(4):864-874. doi: 10.5114/aoms.2016.63259. Epub 2016 Oct 26.

  PMID: 28721155 BACKGROUND

• Horckmans M, Bianchini M, Santovito D, Megens RTA, Springael JY, Negri I, Vacca M, Di Eusanio M, Moschetta A, Weber C, Duchene J, Steffens S. Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis, and Cardiac Function After Myocardial Infarction. Circulation. 2018 Feb 27;137(9):948-960. doi: 10.1161/CIRCULATIONAHA.117.028833. Epub 2017 Nov 22.

  PMID: 29167227 BACKGROUND

• Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN; IRIS Investigators. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus. Circulation. 2017 May 16;135(20):1882-1893. doi: 10.1161/CIRCULATIONAHA.116.024863. Epub 2017 Feb 28.

  PMID: 28246237 BACKGROUND

• Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR; IRIS Trial Investigators. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Apr 7;374(14):1321-31. doi: 10.1056/NEJMoa1506930. Epub 2016 Feb 17.

  PMID: 26886418 BACKGROUND

• Bouchi R, Terashima M, Sasahara Y, Asakawa M, Fukuda T, Takeuchi T, Nakano Y, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa Y. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017 Mar 3;16(1):32. doi: 10.1186/s12933-017-0516-8.

  PMID: 28253918 BACKGROUND

• Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care. 2003 Dec;26(12):3320-5. doi: 10.2337/diacare.26.12.3320.

  PMID: 14633821 BACKGROUND

• Bastarrika G, Broncano J, Schoepf UJ, Schwarz F, Lee YS, Abro JA, Costello P, Zwerner PL. Relationship between coronary artery disease and epicardial adipose tissue quantification at cardiac CT: comparison between automatic volumetric measurement and manual bidimensional estimation. Acad Radiol. 2010 Jun;17(6):727-34. doi: 10.1016/j.acra.2010.01.015. Epub 2010 Apr 3.

  PMID: 20363161 BACKGROUND

• Hindso L, Jakobsen LS, Jacobsen C, Lynnerup N, Banner J. Epicardial adipose tissue volume estimation by postmortem computed tomography of eviscerated hearts. Forensic Sci Med Pathol. 2017 Dec;13(4):468-472. doi: 10.1007/s12024-017-9930-1. Epub 2017 Nov 2.

  PMID: 29098638 BACKGROUND

• Oda S, Utsunomiya D, Funama Y, Yuki H, Kidoh M, Nakaura T, Takaoka H, Matsumura M, Katahira K, Noda K, Oshima S, Tokuyasu S, Yamashita Y. Effect of iterative reconstruction on variability and reproducibility of epicardial fat volume quantification by cardiac CT. J Cardiovasc Comput Tomogr. 2016 Mar-Apr;10(2):150-5. doi: 10.1016/j.jcct.2015.10.006. Epub 2015 Nov 3.

  PMID: 26560351 BACKGROUND

• Ding X, Terzopoulos D, Diaz-Zamudio M, Berman DS, Slomka PJ, Dey D. Automated pericardium delineation and epicardial fat volume quantification from noncontrast CT. Med Phys. 2015 Sep;42(9):5015-26. doi: 10.1118/1.4927375.

  PMID: 26328952 BACKGROUND

• Spearman JV, Renker M, Schoepf UJ, Krazinski AW, Herbert TL, De Cecco CN, Nietert PJ, Meinel FG. Prognostic value of epicardial fat volume measurements by computed tomography: a systematic review of the literature. Eur Radiol. 2015 Nov;25(11):3372-81. doi: 10.1007/s00330-015-3765-5. Epub 2015 Apr 30.

  PMID: 25925354 BACKGROUND

• Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. 2015 Jun;11(6):363-71. doi: 10.1038/nrendo.2015.58. Epub 2015 Apr 7.

  PMID: 25850659 BACKGROUND

• Antoniades C, Shirodaria C, Warrick N, Cai S, de Bono J, Lee J, Leeson P, Neubauer S, Ratnatunga C, Pillai R, Refsum H, Channon KM. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006 Sep 12;114(11):1193-201. doi: 10.1161/CIRCULATIONAHA.106.612325. Epub 2006 Aug 28.

  PMID: 16940192 BACKGROUND

• Margaritis M, Sanna F, Lazaros G, Akoumianakis I, Patel S, Antonopoulos AS, Duke C, Herdman L, Psarros C, Oikonomou EK, Shirodaria C, Petrou M, Sayeed R, Krasopoulos G, Lee R, Tousoulis D, Channon KM, Antoniades C. Predictive value of telomere length on outcome following acute myocardial infarction: evidence for contrasting effects of vascular vs. blood oxidative stress. Eur Heart J. 2017 Nov 1;38(41):3094-3104. doi: 10.1093/eurheartj/ehx177.

  PMID: 28444175 BACKGROUND

• Oikonomou EK, Antoniades C. The role of adipose tissue in cardiovascular health and disease. Nat Rev Cardiol. 2019 Feb;16(2):83-99. doi: 10.1038/s41569-018-0097-6.

  PMID: 30287946 BACKGROUND

• Antonopoulos AS, Sanna F, Sabharwal N, Thomas S, Oikonomou EK, Herdman L, Margaritis M, Shirodaria C, Kampoli AM, Akoumianakis I, Petrou M, Sayeed R, Krasopoulos G, Psarros C, Ciccone P, Brophy CM, Digby J, Kelion A, Uberoi R, Anthony S, Alexopoulos N, Tousoulis D, Achenbach S, Neubauer S, Channon KM, Antoniades C. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017 Jul 12;9(398):eaal2658. doi: 10.1126/scitranslmed.aal2658.

  PMID: 28701474 BACKGROUND

• Kluner LV, Oikonomou EK, Antoniades C. Assessing Cardiovascular Risk by Using the Fat Attenuation Index in Coronary CT Angiography. Radiol Cardiothorac Imaging. 2021 Feb 25;3(1):e200563. doi: 10.1148/ryct.2021200563. eCollection 2021 Feb.

  PMID: 33778665 BACKGROUND

• Patel VB, Shah S, Verma S, Oudit GY. Epicardial adipose tissue as a metabolic transducer: role in heart failure and coronary artery disease. Heart Fail Rev. 2017 Nov;22(6):889-902. doi: 10.1007/s10741-017-9644-1.

  PMID: 28762019 RESULT

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Carlos V Serrano Junior, MD PHD

  InCOR- University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ARO InCOR HC FMUSP

CONTACT

551126615795; aro@incor.usp.br

InCor HC FMUSP

CONTACT

551126615795; aro@incor.usp.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be double-blind, meaning both the research participants and the outcome assessors will be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Doctor

Model Details: Diabetic patients who suffered acute myocardial infarction will be divided into 2 groups, an arm that will receive medication and another arm placebo (control population).

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 16, 2024
• Study Start: September 1, 2024
• Primary Completion: September 1, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

BR (1)