An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin

Type 2 Diabetes Clinical Trial

Official title:

An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02433678
• Other study ID #: 1972
• Status: Completed
• Phase: Phase 4
• Start date: November 2015
• Est. completion date: November 2018

Study information

• Verified date: October 2019
• Source: University at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, prospective, randomized, placebo -controlled, parallel design and double blind study to evaluate oxidative stress, inflammation and hypertension markers and mediators before and after treatment with dapagliflozin.

Description:

Two groups of 26 patients each (total 52 patients) with type 2 diabetes on oral agents will be included in the study. One group will be randomized to dapagliflozin (a dose of 5 mg daily will be titrated to 10 mg daily during the first week) while the other will be placebo. The patients will be treated for 12 weeks. Only half the patients (equal numbers in both groups) will be tested for the secondary endpoints related to postprandial and single dose induced changes. The primary endpoint of the study is to detect a significant difference in the percent change in fasting Nuclear factor-k B (NFκB) activation (DNA binding activity) in mononuclear cells (MNC) before and after dapagliflozin use (0 week vs. 12 weeks) as compared to placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 20-80 years inclusive.

• Type 2 diabetes

• BMI =30 kg/m2

• Subjects on statins, ACE inhibitors, ARBs, thiazolidinediones and -antioxidants will be allowed as long as they are on stable doses of these -compounds and the dosage in not changed during the course of study. -Patients will be evenly distributed between the 2 groups based on statins, -ARBs, TZDs and ACE inhibitors use.

• HbA1c = 8.0%

Exclusion Criteria:

• Use of GLP-1 agonists or DPP-IV or SGLT-2 inhibitors therapy in the last 3 -months.

• Risk for pancreatitis, i.e., history of gallstones, alcohol abuse, and -hypertriglyceridemia.

• Coronary event or procedure (myocardial infarction, unstable angina, coronary -artery bypass, surgery or coronary angioplasty) in the previous 3 months.

• Hepatic disease: Severe hepatic insufficiency and/or significant abnormal liver -function defined as:

• aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or -alanine aminotransferase (ALT) >3x ULN

• Total bilirubin >2.0 mg/dL (34.2 µmol/L)

• Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody

• (liver function tests more than 3 times the upper limit of normal)

• Renal impairment (serum eGFR <60 ml/min)

• Any other life-threatening, non-cardiac disease

• Uncontrolled hypertension (BP > 160/100 mm of Hg)

• Congestive Heart Failure class III or IV.

• Use of an investigational agent or therapeutic regimen within 30 days of study

• Participation in any other concurrent clinical trial

• pregnant or breastfeeding patients

• Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• dapagliflozin
SGLT-2 inhibitor for the treatment of type 2 diabetes
• Placebo

Locations

Country	Name	City	State
United States	ECMC Ambulatory Center, 3rd Floor	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
University at Buffalo	Kaleida Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Hypertension Mediators	Plasma concentrations measurement of Angiotensinogen through enzyme-linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurement of Angitosensin II through enzyme-linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurement of Renin through enzyme-linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurement of Atrial natriuretic peptide through enzyme linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurement of B-type natriuretic peptide through enzyme linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurement of Cyclic guanosine monophosphate through enzyme linked immunosorbent assay	12 weeks
Other	Change in Hypertension Mediators	Plasma concentration measurment of Cyclic adenosine monophosphate through enzyme linked immunosorbent assay	12 week
Primary	Difference in the Percent Change in Fasting Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells Activation (DNA Binding Activity) in Mononuclear Cells Before and After Dapagliflozin Use	nuclear factor kappa-light-chain-enhancer of activated B cells measurement through Transcription factor assay	12 weeks
Secondary	Changes in Expression of Inflammatory Mediators	p47phox in mononuclear cells through real time polymerase chain reaction	12 Weeks
Secondary	Changes in Expression of Inflammatory Mediators	Suppressor Of Cytokine Signaling 3 measurement in Mononuclear cells through real time polymerase chain reaction	12 weeks
Secondary	Changes in Expression of Inflammatory Mediators	Interleukin 1 Beta measurement in mononuclear cells through real time polymerase chain reaction	12 weeks
Secondary	Changes in Expression of Inflammatory Mediators	c-Jun N-terminal kinase 1 measurement in Mononuclear cells through real time polymerase chain reaction	12 weeks
Secondary	Changes in Expression of Inflammatory Mediators	Toll-like receptor 4 measurement in mononuclear cells through real time polymerase chain reaction	12 weeks
Secondary	Changes in Expression of Inflammatory Mediators	Tumor necrosis factor alpha measurement in mononuclear through real time polymerase chain reaction	12 weeks