Novel Therapeutics and Endothelial Dysfunction in T1DM Patients (ENDIS)

Impact of Additional Treatment With Empagliflozin or Semaglutide on Endothelial Function and Other Clinical Parameters and Biomarkers in T1DM Patients

The aim of study is impact of additional treatment with new antidiabetic drugs (semaglutide or empagliflozine) compared to control group in T1DM patients - impact on endothelial function measured by FMD and FPF, arterial stiffness - measured by PWV, inflammatory biomarkers, markers of oxidative stress and endothelial progenitor cells (CD 34+/VDRL2, CD 133+/VDRL2) and correlation with glucovariability or time in range, measured with CGM system.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Biomarkers; Endothelial Dysfunction; Arterial Stiffness; FMD; Incretins; Endothelial Progenitor Cells; SGLT 2 Inhibitors; Glucose Excursions; FPF
• Intervention / Treatment: Drug: Semaglutide Pen Injector [Ozempic]; Drug: Empagliflozin 10 MG

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Slovenia
  • Celje, Slovenia, 3000
    • General Hospital Celje

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• T1DM
• HbA1C<=9%
• prone to CGM system
• 20 - 70 years

Exclusion Criteria:

• HbA1C >9%,
• BMI<22,
• pregnancy or lactation,
• known hypersensitivity to study drug,
• malignant disease ( excluded >5 years disease free, bazocellular or planocellular ca of skin),
• liver cirrhosis child C,
• eGFR<60 ml/min,
• chronic inflammatory disease,
• proliferative diabetic rethinopathy,
• MEN or medullary thyroid cancer in familly,
• concomitant drugs with influence on glycemia and antiinflammatory influence (corticosteroids, immunosupresive therapy),
• Major cardiovascular event last 2 months ( stroke, MI)

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GLP 1 agonist; semaglutide in titrating doses 0,25 to 1,0 mg - duration of treatment12 weeks adding to insulin sheme (MDI or CII)	Drug: Semaglutide Pen Injector [Ozempic]; GLP 1 agonist
Active Comparator: SGLT 2 inhibitor; empagliflozin 25 mg - duration of treatment 12 weeks adding to insulin sheme (MDI or CII or hybride system)	Drug: Empagliflozin 10 MG; SGLT 2 inhibitor
No Intervention: comparator; continuing treatment only with insulin sheme (MDI or CII or hybride system)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of endothelial function by flow mediated dilation (FMD) of brachial artery	measurement of dilation of brachial artery (in %) before and after postishemic hyperemia comparing two therapeutic groups and control group before and after intervention	12 weeks
evaluation of endothelial function by strain gauge plethysmography as change in forearm blood flow	changes in tissue perfusion (ml/100 ml of tissue/min) measured with strange gauge plethysmography as formarm blood flow before and after postishemic reactive hyperemija comparing two therapeutic groups and control group before and after intervention	12 weeks
evaluation of arterial stiffness with peak wave velocity ( PWV)	measurements of the velocity (m/s) at which arterial blood pressure pulses propagate - comparing two therapeutic groups and control group before and after intervention	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of change in inflammatory biomarkers	change of hs CRF, Il6 after treatment comparing two therapeutic groups and control	12 weeks
evaluation of change in biomarkers of endothelial dysfunction	change in s-VCAM, s-ICAM values before and after intervention - comparing two therapeutic groups and control	12 weeks
evaluation of endothelial progenitor cells EPC count	change in count of endothelial progenitor cells CD 34*, 133+ as endothelial function markers before and after intervention - comparing two therapeutic groups and control	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
body impedance measurements	changes in measurements of body composition fat , muscle and water before and after intervention - comparing two therapeutic groups and control	12 weeks
changes of glycemia endpoints glucovariability/time in range	variability of excursions of glucose - coeficient of variability / time in range defined as blood glucose beetwen 3,9 and 10 mmol/l before and after drug intervention assesed with CGM system	2 weeks

Collaborators and Investigators

• Sponsor: General and Teaching Hospital Celje
• Investigators: Study Chair: Andrej Janez, prof PhD, General and teaching hospital Celje and UKC Ljubljana/Maribor

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2021
• Primary Completion (Actual): March 10, 2022
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 0120-63-2020

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
• product manufactured in and exported from the U.S.: No