Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment (DEMETER)

Efficacy of Double vs Standard Empapagliflozin Dose for METabolic syndromE tReatment (DEMETER - SIRIO 11) Study

The DEMETER - SIRIO 11 study is a phase III, multicenter, randomized, open-labled, investigator-initiated clinical trial with a 6 month follow-up.

The study population will include 200 subjects with diagnosis of metabolic syndrome.

All enrolled patients (nn=200) will be randomly assigned in 1:1 ratio to one of the two study arms:

1. Empagliflozin 20 mg - experimental arm
2. Empagliflozin 10 mg - control arm. Primary co-endpoints of the study include: BMI and HbA1c. Secondary endpoints include: LDL-C, triglycerides, CRP, NT-proBNP, LVEF (echocardiography), body composition, VO2max (ergospirometry), waist-hip ratio (WHR), liver steatosis assessment (LSA) by computed tomography (CT), major adverse cardiovascular events - MACE (based on medical history: heart attack, stroke, death), cardiovascular hospitalizations.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: Empagliflozin 20 mg; Drug: Empagliflozin 10 mg

Detailed Description

The DEMETER - SIRIO 11 study is a phase III, multicenter, randomized, open-labled, investigator-initiated clinical trial with a 6 month follow-up.

The study population will include 200 subjects with diagnosis of metabolic syndrome.

All enrolled patients (nn=200) will be randomly assigned in 1:1 ratio to one of the two study arms:

1. Empagliflozin 20 mg - experimental arm
2. Empagliflozin 10 mg - control arm.

Primary co-endpoints of the study include: BMI and HbA1c.

Secondary endpoints include:

• LDL-C,
• triglycerides,
• CRP,
• NT-proBNP,
• LVEF (echocardiography),
• body composition,
• VO2max (ergospirometry),
• waist-hip ratio (WHR),
• liver steatosis assessment (LSA) by computed tomography (CT),
• major adverse cardiovascular events - MACE (based on medical history: heart attack, stroke, death),
• cardiovascular hospitalizations.

Other variables that are scheduled to be analyzed: central arterial pressure, pulse wave propagation speed, ABPM (ambulatory blood pressure monitoring), endothelial function assessment by Endopath, autonomic nervous system assessment (ANSA) by Task Force Touch CARDIO (TFTC), exercise tolerance, thickness of the adipose tissue (skin fold), blood samples: blood count, serum creatinine and eGFR, ALT, AST, GGTP, total cholesterol, HDL-C, uric acid, plasma concentration of calcium, phosphate, parathormon, 25-OH-D3, cystatin C, erythropoietin; morning urine: N-acetyl-beta-D-glucosaminidase, sodium/creatinine ratio, calcium/creatinine ratio, albumin/creatinine ratio. Moreover, functioning in chronic disease and adherence to medication and diet will be assessed with dedicated questionairies (FCIS, ACDS, ACDS diet).

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jacek Kubica, Prof.; Phone Number: +48 525854023; Email: jkubica@cm.umk.pl

Study Locations

• Poland
  • Cuiavian-Pomeranian
    • Bydgoszcz, Cuiavian-Pomeranian, Poland, 85-094
      • Recruiting
      • Cardiology Department, Dr. A. Jurasz University Hospital
      • Contact: Jacek Kubica, prof.; Phone Number: +48525854023; Email: jkubica@cm.umk.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosis of metabolic syndrome as follows: the presence of obesity (waist circumference ≥ 88 cm in women; ≥102 cm or body mass index (BMI) ≥30 kg/m2) and two of the three following criteria:

  1. high blood pressure (systolic blood pressure - in-office measurement: ≥ 130 and/or diastolic blood pressure ≥85 mm Hg or systolic blood pressure - ambulatory measurement: ≥130 and/or diastolic blood pressure ≥ 80 mm Hg) or on anti-hypertensive treatment;
  2. impaired glucose metabolism (fasting glucose ≥100 mg/dL or ≥ 140 mg/dL after 120 min in oral glucose tolerance test or HbA1c ≥5.7%) or on glucose-lowering drug treatment;
  3. elevated non-high-density lipoprotein (non-HDL ≥130 mg/dL) cholesterol level (atherogenic dyslipidemia) or on lipid-lowering drug treatment

Exclusion Criteria:

• current treatment with SGLT2 inhibitor
• chronic kidney disease with estimated glomerular filtration rate (eGFR) < 30 mL/min or on dialysis
• severely impaired liver function
• known hypersensitivity to the active empagliflozin or to any of the excipients contained in Jardiance
• history of ketoacidosis
• diabetes treated with insulin
• pregnancy
• decompensated heart failure
• acute coronary syndrome
• active thromboembolic disease
• current treatment for neoplastic disease
• active inflammatory disease within 1 month prior to enrollment
• expected lifetime <1 year
• non-cooperative patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin 20 mg; Patients receiving empagliflozin 20 mg daily	Drug: Empagliflozin 20 mg; Patients receiving empagliflozin 20 mg daily - experimental arm
Active Comparator: Empagliflozin 10 mg; Patients receiving empagliflozin 10 mg daily	Drug: Empagliflozin 10 mg; Patients receiving empagliflozin 10 mg daily - control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI (Body Mass Index)	change in BMI between study arms	0-6 months
concentration of HbA1c (glycated hemoglobin)	change in glycated hemoglobin plasma concentration between study arms	0-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
concentration of LDL-C (low density cholesterol serum concentration)	change in low density cholesterol serum concentration between study arms	0-6 months
concentration of triglycerides	change in triglycerides serum concentration between study arms	0-6 months
concentration of CRP (c-reactive protein)	change in CRP serum concentration between study arms	0-6 months
concentration of NT-proBNP	change in NT-pro BNP serum concentration between study arms	0-6 months
LVEF - left ventricle ejection fraction (echocardiography)	change in LVEF (presented in percentage) between study arms	0-6 months
body composition analysis - body fat mass [kg]	evaluation of body fat mass [kg] change throughout the study	0-6 months
body composition analysis - body fat mass [%]	evaluation of body fat mass [%] change throughout the study	0-6 months
body composition analysis - lean body mass [kg]	evaluation of lean body mass [kg] change throughout the study	0-6 months
body composition analysis - lean body mass [%]	evaluation of lean body mass [%] change throughout the study	0-6 months
body composition analysis - skeletal muscle mass [kg]	evaluation of skeletal muscle mass [kg] change throughout the study	0-6 months
body composition analysis - total body water [liters]	evaluation of total body water [liters] change throughout the study	0-6 months
body composition analysis - total body water [%]	evaluation of total body water [%] change throughout the study	0-6 months
body composition analysis - extracellular water [liters]	evaluation of extracellular water [liters] change throughout the study	0-6 months
body composition analysis - extracellular water [%]	evaluation of extracellular water [%] change throughout the study	0-6 months
body composition analysis - hydration [%]	evaluation of hydration [%] change throughout the study	0-6 months
body composition analysis - visceral fat level [liters]	evaluation of visceral fat level [liters] change throughout the study	0-6 months
level of maximal oxygen uptake (VO2max) measured in ergospirometry	change in VO2 max between study arms	0-6 months
waist-hip ratio (WHR)	change in waist-hip ratio between study arms	0-6 months
liver steatosis assessment (LSA) by computed tomography (CT)	evaluation of liver steatosis assessment (LSA) assessed with computed tomography (CT), between study arms throughout the study	0-6 months
major adverse cardiovascular events - MACE	rate of MACE (based on medical history: heart attack, stroke, death) between study arms throughout the study	0-6 months
cardiovascular hospitalizations	rate of cardiovascular hospitalizations between study arms	0-6 months

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Jacek Kubica, Prof., Collegium Medicum w Bydgoszczy

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: adherence; metabolic syndrome; empagliflozin
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: DEMETER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No