Effect of Sodium Glucose Co-transporter 2 Inhibitor on Inflammatory Cytokine in Type 2 Diabetes

Sponsor
Yonsei University (Other)
Overall Status
Completed
CT.gov ID
NCT02964572
Collaborator
(none)
61
1
2
8
7.7

Study Details

Study Description

Brief Summary

  • Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot

  • Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy

  • Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

First among cardiovascular (CV) end point trials of glucose-lowering agents, the EMPA-REG OUTCOME trial-using 10 or 25 mg/day SGLT2 inhibitor empagliflozin against placebo in 7,020 patients with T2DM who were at increased CV risk-reported a 14% reduction in major CV events and marked relative risk reductions in CV mortality (38%), hospitalization for heart failure (35%), and death from any cause (32%) over a median time period of 2.6 years. Though these results have raised the possibility that mechanisms other than those observed in the trial-modest improvement in glycemic control, small decrease in body weight, and persistent reductions in blood pressure and uric acid level-may be at play, it's not clearly known yet.

The inflammatory nature of atherosclerosis is well established. We hypothesized that empagliflozin might have an inhibitory effect on inflammasome activity in macrophages, thus contribute to cardioprotective effects in diabetes.

  • Single-center, prospective, active-controlled, open, randomized, 2 arm parallel, interventional, exploratory pilot

  • Type 2 diabetic patients with high cardiovascular risks who have inadequate glycaemic control with metformin-based oral hypoglycemic agents will be prescribed glimepiride (comparison group) or empagliflozin (study group) for 60 days (plus or minus 32 days) as add-on therapy

  • Changes in IL-1beta secretion, serum beta-hydroxybutyrate concentration, and NLRP3 inflammasome activity from baseline to final timepoint will be assessed

  • Healthy volunteers : effect of 3 day-ketogenic diet on changes in cytokines, metabolites (IL-1beta, beta-hydroxybutyrate , etc) and inflammasome activity in macrophages

Study Design

Study Type:
Interventional
Actual Enrollment :
61 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Actual Study Start Date :
Nov 1, 2016
Actual Primary Completion Date :
Jul 1, 2017
Actual Study Completion Date :
Jul 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Glimepiride

Glimepiride (anti-diabetic drug) as a comparison group

Drug: Glimepiride
In accordance with the standard treatment guidelines of diabetes, glimepiride as a drug of active comparator will be administered to improve blood sugar in patients with poorly controlled blood sugar.
Other Names:
  • Amaryl
  • Experimental: Empagliflozin

    Empagliflozin (anti-diabetic drug) as a study group

    Drug: Empagliflozin
    Empagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar.
    Other Names:
  • Jardiance
  • Outcome Measures

    Primary Outcome Measures

    1. changes in the secretion of IL-1 beta from peripheral blood mononuclear cells [Day 60]

      The effect of empagliflozin on the secretion of IL-1beta from peripheral blood mononuclear cells

    Secondary Outcome Measures

    1. Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    2. Changes in serum concentrations of beta-hydroxybutyrate, before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    3. Changes in body weight (kg), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    4. Changes in serum concentrations of insulin (µU/mL), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    5. Changes in serum concentrations of glucagon (pg/mL), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    6. Changes in serum concentrations of free fatty acid (μEq/L), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    7. Changes in serum glycated albumin (%), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    8. Changes in serum concentrations of glucose (mg/dL), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    9. Changes in serum concentrations of uric acid (mg/dL), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    10. Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    11. Changes in serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol (mg/dL)), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    12. Changes in serum concentrations of creatinine (mg/dL), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    13. Changes in spot urine concentrations of glucose (mg/dL) and creatinine (mg/dL) (those will be combined to report spot urine glucose-to-creatinine ratio in mg/mg), before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    14. Changes in mRNA expression level (PCR, fold) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    15. Changes in protein expression pattern (western blot, relative to control) of IL-1beta, TNF-alpha, and NLRP3 in peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride [Day 60 plus or minus 32 days]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Age ≥19 years

    • inadequate glycaemic control : HbA1c ≥6.5% or fasting glucose >120 mg/dl or random glucose >180 mg/dl

    • High risk of cardiovascular events defined as the presence of ≥1 of the following:

    1. History of myocardial infarction

    2. Evidence of multi-vessel coronary artery disease

    3. Evidence of single-vessel coronary artery disease with a positive non-invasive stress test for ischemia or history of hospitalization for unstable angina

    4. History of stroke

    5. Evidence of occlusive peripheral artery disease

    6. Evidence of carotid atherosclerosis

    7. Metabolic syndrome

    • Healthy volunteers
    Exclusion Criteria:
    • Type 1 diabetes

    • Organ transplantation

    • Pregnant women

    • eGFR <45

    • Cortisol or growth hormone deficiency, pituitary diseases

    • Gastric surgery

    • Hematologic disorders

    • Active cancers

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center Seoul Korea, Republic of 03722

    Sponsors and Collaborators

    • Yonsei University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Yonsei University
    ClinicalTrials.gov Identifier:
    NCT02964572
    Other Study ID Numbers:
    • 4-2016-0795
    First Posted:
    Nov 16, 2016
    Last Update Posted:
    Aug 27, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 27, 2020