Clinical trial NCT03693560: Effect of Adding Vildagliptin vs Glimepiride to Metformin on Inflammation's Markers in Type-2 Diabetic Patients With CAD
Official title: The Effect of Adding Vildagliptin Versus Glimepiride to Metformin on Markers of Inflammation, Thrombosis, and Atherosclerosis in Diabetic Patients With Symptomatic Coronary Artery Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Diabetes Mellitus, Type 2
Lead sponsor: Damanhour University
Sponsor class: OTHER
Collaborators: name: Tanta University
First posted: 2018-10-03
Enrollment: 80
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All enrolled patients will be mentioned as two groups; Group I (n=40) are patients who the endocrinologist prescribed them vildagliptin plus their metformin to control their blood sugar level. Group II (n=40) are patients who the endocrinologist prescribed them glimepiride plus their metformin.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of adding Vildagliptin versus Glimepiride to Metformin on markers of inflammation, thrombosis, and atherosclerosis in diabetic patients with symptomatic Coronary artery diseases.

The pre-specified established biological markers of inflammation, thrombosis, and atherosclerosis will include: Interleukin 1 beta (IL-1 beta)), hs-CRP, Atherogenic index and coronary risk index, Lipid profile. and adiponectin levels..

Detailed description: The study is designed as a single-center, randomized, double-blinded, clinical trial to provide evidence on the effects of vildagliptin on key biomarkers of atherothrombosis and inflammation. The investigators plan to prospectively enroll 80 patients with proven coronary artery disease ,Diabetes type2 and randomize them in a 1:1 ratio to either vildagliptin-metformin therapy (n=40) or glimepiride /metformin therapy (n=40).

1. All participants agreed to take part in this clinical study and provide informed consent.
2. Patients with Coronary artery diseases.and uncontrolled Diabetes type2 who's taking metformin only will be enrolled (n=80) from endocrinology clinic at Alexandria Armed Forces hospital.
3. Complete physical, laboratory, radiological assessment will be done for all patients to exclude any signs of inflammation or thrombosis.
4. Serum samples will be collected for measuring the biomarkers.
5. All enrolled patients will be mentioned as two groups; Group I (n=40) are patients who the endocrinologist prescribed them vildagliptin plus their metformin to control their blood sugar level. Group II (n=40) are patients who the endocrinologist prescribed them glimepiride plus their metformin.
6. All patients will be followed up during 3 months' period.
7. At the end of 3 months on the new regimen, steps 4 and 5 will be repeated.
8. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
9. Measuring outcome: The primary outcome is the change of serum levels of the measured inflammatory markers after 3 months.
10. Results, conclusion, discussion and recommendations will be given.

Eligibility criteria: Inclusion Criteria:

* Adult patients with Type II-diabetes mellitus on metformin who are planned to be managed with vildagliptin or glimepiride plus metformin at the time of inclusion.
* Symptomatic Coronary Artery Diseases. (\>30 days).

Exclusion Criteria:

* Hepatic impairment.
* Active malignancy.
* Planned surgical intervention.
* Any signs of hypersensitivity or contraindication to study drugs developed.
* Any patient with any signs of active infection or thrombosis at the time of assessment.
* Addition of any antidiabetic medications or insulin during follows up.
* Chronic inflammatory disease (i.e. inflammatory bowel disease, lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection).
* Clinically advanced congestive heart failure - New York Heart Association III-IV
* Severe left ventricular dysfunction (LVEF\<30%) with New York Heart Association II or any New York Heart Association class with documented recent heart failure decompensation (\<3 months)
* Severe stable cardiac angina Community Competence Scale III - IV or Unstable angina
* Pregnancy, lactation or child-bearing potential.

Primary outcomes:
measure: Change in markers of athero-thrombosis and inflammation ( interleukin (IL)-1 beta).
timeFrame: Baseline and 3 months
measure: Change in High sensitivity C-reactive protein (hsCRP) level.
timeFrame: Baseline and 3 months
measure: Change in Adiponectin level.
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Change in Lipid profile
timeFrame: Baseline and 3 months
measure: Percent Change in ( Low-density lipoprotein (LDL) cholesterol / High-density lipoprotein (HDL) cholesterol ) for each patient before and after 3 months combination treatment for each group .
timeFrame: Baseline and 3 months
measure: Change in Hemoglobin A1c (HbA1c).
timeFrame: Baseline and 3 months
measure: Percent Change in (total cholesterol / High-density lipoprotein (HDL) cholesterol) for each patient before and after 3 months combination treatment for each group .
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Damanhūr
country: Egypt
facility: Faculty of Pharmacy - Damanhour University.
Study officials:
affiliation: Faculty of Pharmacy - Damanhour University.
name: Gamal Omran, PhD
role: STUDY_DIRECTOR
affiliation: Tanta University
name: Tarek Mostafa, PhD
role: STUDY_DIRECTOR
affiliation: Alex.Armed Forces Hospital.
name: Ahmed skokry, PhD
role: STUDY_DIRECTOR
affiliation: Faculty of Pharmacy - Damanhour University.
name: Rehab Werida, PhD
role: STUDY_DIRECTOR
affiliation: Faculty of Pharmacy - Damanhour University
name: Mahmoud kabel
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Younis A, Eskenazi D, Goldkorn R, Leor J, Naftali-Shani N, Fisman EZ, Tenenbaum A, Goldenberg I, Klempfner R. The addition of vildagliptin to metformin prevents the elevation of interleukin 1ss in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study. Cardiovasc Diabetol. 2017 May 22;16(1):69. doi: 10.1186/s12933-017-0551-5.
citation: Derosa G, Maffioli P, Ferrari I, Mereu R, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D'Angelo A, Salvadeo SA. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res. 2010 Aug;42(9):663-9. doi: 10.1055/s-0030-1255036. Epub 2010 Jun 17.
citation: Kazemi T, Hajihosseini M, Moossavi M, Hemmati M, Ziaee M. Cardiovascular Risk Factors and Atherogenic Indices in an Iranian Population: Birjand East of Iran. Clin Med Insights Cardiol. 2018 Feb 20;12:1179546818759286. doi: 10.1177/1179546818759286. eCollection 2018.
citation: El-Mesallamy HO, Hamdy NM, Salman TM, Mahmoud S. Adiponectin and E-selectin concentrations in relation to inflammation in obese type 2 diabetic patients with coronary heart disease(s). Minerva Endocrinol. 2011 Sep;36(3):163-70.
citation: Werida R, Kabel M, Omran G, Shokry A, Mostafa T. Comparative clinical study evaluating the effect of adding Vildagliptin versus Glimepiride to ongoing Metformin therapy on diabetic patients with symptomatic coronary artery disease. Diabetes Res Clin Pract. 2020 Dec;170:108473. doi: 10.1016/j.diabres.2020.108473. Epub 2020 Sep 28.