Type2 Diabetes MellitusNCT02964572
Effect of Sodium Glucose Co-transporter 2 Inhibitor on Inflammatory Cytokine in Type 2 Diabetes
A study testing Glimepiride and Empagliflozin in people with Type2 Diabetes Mellitus, run by Yonsei University at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Type2 Diabetes Mellitus
- What is being tested?
- Glimepiride and Empagliflozin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteSouth Korea
- Study dates
- Nov 2016to Jul 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- History of myocardial infarction
- Evidence of multi-vessel coronary artery disease
- Evidence of single-vessel coronary artery disease with a positive non-invasive stress test for ischemia or history of hospitalization for unstable angina
Show all 11Show fewer
- History of stroke
- Evidence of occlusive peripheral artery disease
- Evidence of carotid atherosclerosis
- Metabolic syndrome
- Healthy volunteers
Who cannot join
- Type 1 diabetes
- Organ transplantation
- Pregnant women
- eGFR <45
- Cortisol or growth hormone deficiency, pituitary diseases
- Gastric surgery
- Hematologic disorders
- Active cancers
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Yonsei University College of Medicine, Department of Internal Medicine, Division of Endocrinology, Severance Hospital, Diabetes center
Seoul, 03722
About this study
- 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.
Read the 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
- Conditions
- Type2 Diabetes Mellitus
- Being tested
- Glimepiride, Empagliflozin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlimepirideDrug
Also called Amaryl
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.
EmpagliflozinDrug
Also called Jardiance
Empagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar.
| Study group | Role | What they receive |
|---|---|---|
| Glimepiride | Active comparator | Glimepiride (anti-diabetic drug) as a comparison group Receives: Drug: Glimepiride |
| Empagliflozin | Experimental | Empagliflozin (anti-diabetic drug) as a study group Receives: Drug: Empagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
changes in the secretion of IL-1 beta from peripheral blood mononuclear cells
The effect of empagliflozin on the secretion of IL-1beta from peripheral blood mononuclear cells
Measured: Day 60
Secondary outcomes (15)
Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of beta-hydroxybutyrate, before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in body weight (kg), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of insulin (µU/mL), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of glucagon (pg/mL), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of free fatty acid (μEq/L), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum glycated albumin (%), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of glucose (mg/dL), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of uric acid (mg/dL), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol (mg/dL)), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
Changes in serum concentrations of creatinine (mg/dL), before and after the administration of empagliflozin or glimepiride
Measured: Day 60 plus or minus 32 days
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
Measured: Day 60 plus or minus 32 days
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
Measured: Day 60 plus or minus 32 days
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
Measured: Day 60 plus or minus 32 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02964572
- Sponsor's protocol ID
- 4-2016-0795
- Status last verified
- Aug 2020
- First submitted
- 11 Nov 2016
- Last updated
- 27 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Kim ER, Kim SR, Cho W, Lee SG, Kim SH, Kim JH, Choi E, Kim JH, Yu JW, Lee BW, Kang ES, Cha BS, Lee MS, Cho JW, Jeon JY, Lee YH. Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21. Front Immunol. 2022 Apr 28;13:843520. doi: 10.3389/fimmu.2022.843520. eCollection 2022.
PubMed 35572519
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sodium Glucose Co-transporter 2 Inhibitor on Inflammatory Cytokine in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02964572
- Acronym / sponsor ID
- 4-2016-0795
- Conditions
- Type2 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Nov 2016 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glimepiride | Active comparator | Drug: GlimepirideGlimepiride (anti-diabetic drug) as a comparison group |
| Empagliflozin | Experimental | Drug: EmpagliflozinEmpagliflozin (anti-diabetic drug) as a study group |
Who may qualify
- Ages
- 19 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Healthy volunteers
Key exclusion criteria (8 listed)
- Type 1 diabetes
- Organ transplantation
- Pregnant women
- eGFR <45
- Cortisol or growth hormone deficiency, pituitary diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlimepirideAlso: AmarylIn 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. | Drug | Glimepiride |
| EmpagliflozinAlso: JardianceEmpagliflozin as a drug of experimental will be administered to improve blood sugar in patients with poorly controlled blood sugar. | Drug | Empagliflozin |
Primary outcome
changes in the secretion of IL-1 beta from peripheral blood mononuclear cells
Time frame: Day 60
The effect of empagliflozin on the secretion of IL-1beta from peripheral blood mononuclear cells
15 secondary outcomes
Changes in the secretion of TNF-alpha from peripheral blood mononuclear cells, before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of beta-hydroxybutyrate, before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in body weight (kg), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of insulin (µU/mL), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of glucagon (pg/mL), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of free fatty acid (μEq/L), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum glycated albumin (%), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of glucose (mg/dL), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of uric acid (mg/dL), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of liver enzymes (aspartate aminotransferase and alanine aminotransferase (IU/L)), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol (mg/dL)), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
Changes in serum concentrations of creatinine (mg/dL), before and after the administration of empagliflozin or glimepiride
Time frame: Day 60 plus or minus 32 days
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
Time frame: Day 60 plus or minus 32 days
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
Time frame: Day 60 plus or minus 32 days
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
Time frame: Day 60 plus or minus 32 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2020.
- Derived from this study: PubMed 35572519Kim ER, Kim SR, Cho W, Lee SG, Kim SH, Kim JH, Choi E, Kim JH, Yu JW, Lee BW, Kang ES, Cha BS, Lee MS, Cho JW, Jeon JY, Lee YH. Short Term Isocaloric Ketogenic Diet Modulates NLRP3 Inflammasome Via B-hydroxybutyrate and Fibroblast Growth Factor 21. Front Immunol. 2022 Apr 28;13:843520. doi: 10.3389/fimmu.2022.843520. eCollection 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glimepiride and Empagliflozin in people with Type2 Diabetes Mellitus, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
changes in the secretion of IL-1 beta from peripheral blood mononuclear cells (time frame: Day 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02964572, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2020.