NCT06557811

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

Effect of Oral Semaglutide on Epicardial and Pericoronary Adipose Tissues in Type 2 Diabetes After Myocardial Infarction: a Randomized and Double-blind Clinical Trial

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 88 (estimated)
• Sponsor: University of Sao Paulo General Hospital · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

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.

Detailed description

TITLE: Effect of Oral Semaglutide on Epicardial and Pericoronary Adipose Tissues in Type 2 Diabetic Patients After Myocardial Infarction. OBJECTIVE: This randomized, placebo-controlled study primarily aims to demonstrate the effect of oral semaglutide on pericardial and pericoronary adipose tissues, atherosclerotic plaque, and the vascular lumen in patients with T2D after myocardial infarction through CCT and CTA analysis, with a secondary objective of analyzing anthropometric markers, cardiac markers, and insulin resistance. MATERIAL AND METHODS: Equipment: Cardiac Computed Tomography (CCT) and Echocardiography: A standard CTA protocol using a 320 detector-row scanner (Aquillion ONE, Canon Medical Systems, Ottawa, Japan), including coronary calcium score (CCS) and CTA, will be performed. To achieve a heart rate \< 65 bpm during acquisition, patients will receive oral metoprolol (50-100 mg) or intravenous metoprolol (up to 15 mg in 5 mg increments). Fast-acting sublingual nitrate (2.5-5 mg) will also be administered to all patients before scanning. After CCS acquisition, ECG-triggered CTA will be performed with 70 mL of non-ionic contrast (Iopromide 370 mg iodine/mL, Bayer Schering Pharma, Berlin, Germany), injected intravenously at 5.0 mL/s, followed by 30-40 mL of saline. The CTA parameters are as follows: collimation 0.5 mm, rotation time 400 ms, tube voltage and current 100-120 kV and 250-550 mA, adjusted to body mass index. To be performed during Visits 1 and 2: * Coronary Computed Tomography Angiography (CTA) in the proximal segment of the right coronary artery and/or anterior descending coronary artery. * Cardiac Markers: Troponin I, CK-MB, C-Reactive Protein, Interleukin 6. * Metabolic Markers: Measurement of neck circumference, hepatic steatosis (Abdominal Ultrasound), Fasting Glycemia, HbA1c, Basal Insulin and HOMA-IR, Cystatin C, Total Cholesterol and Fractions, Uric Acid, TSH and Free T4. * Anthropometric and Clinical Markers: Body Weight, Body Mass Index (BMI) = weight / height², Abdominal Waist (AW), AW/Height Ratio, Blood Pressure, and Heart Rate. STUDY DESIGN: Prospective, placebo-controlled, double-blind, single-center randomized study with 4 phases: First phase: Screening of chronic patients who had AMI with T2D for more than 1 month and less than 6 months in the InCor database, according to inclusion criteria. The patient will be called for Visit 1 (inclusion). If the screening is successful, the patient will be fully informed about this study and will read and freely sign the Informed Consent Form (ICF). After this, a clinical consultation will be conducted, anthropometric data, blood pressure, and heart rate will be measured, and the exams of CCT, CTA, Abdominal Ultrasound, Echocardiography, and other markers described will be ordered to enter the 1st phase of the study and receive randomized oral semaglutide/placebo treatment on the day of Visit 1. Randomization: The start of randomization will be considered as day one. The other phases will be counted from the start of randomization. Phone calls during the 2nd and 3rd phases will ask the following questions: 1) Is the patient using the medication correctly? If not, the patient will be invited for an extra visit. 2) Is the patient experiencing any Adverse Events (AE)? If yes, the patient will be invited for an extra visit. 4th Phase (Visit 2): It will be asked if the patient used the medication/placebo correctly, if any AE occurred, a clinical consultation will be conducted, and the exams of CCT, CTA, Abdominal Ultrasound, Echocardiography, and other described markers will be ordered. STATISTICAL ANALYSIS: Qualitative characteristics will be described according to the groups using absolute and relative frequencies, and the association between groups will be verified at Visit 1 using chi-square tests or exact tests. Quantitative characteristics will be described according to the groups using summary measures (mean, standard deviation, median, minimum, and maximum) and compared at baseline using Student's t-test or Mann-Whitney tests according to the probability distribution of the data. The characteristics of interest will be described according to the groups throughout the follow-up using summary measures and compared between groups and evaluation moments using generalized estimation equations with appropriate distributions and linkages, followed by Bonferroni multiple comparisons when necessary. IBM-SPSS for Windows version 22.0 software will be used for the analysis, and Microsoft Excel 2010 software will be used for data tabulation. Tests will be performed with a significance level of 5%.

Conditions

• Diabetic Patients
• Acute Myocardial Infarction

Interventions

Type	Name	Description
DRUG	Semaglutide	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.

Timeline

• Start date: 2024-09-01
• Primary completion: 2024-09-01
• Completion: 2026-09-01
• First posted: 2024-08-16
• Last updated: 2024-08-26

Locations

1 site across 1 country: Brazil