Clinical trial NCT02433678: An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin
Official title: An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Lead sponsor: University at Buffalo
Sponsor class: OTHER
Collaborators: name: Kaleida Health
First posted: 2015-05-05
Enrollment: 52
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 Weeks
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 weeks
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 weeks
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 weeks
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 weeks
measure: Changes in Expression of Inflammatory Mediators
timeFrame: 12 weeks
Other outcomes:
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 weeks
measure: Change in Hypertension Mediators
timeFrame: 12 week
Locations:
city: Buffalo
country: United States
facility: ECMC Ambulatory Center, 3rd Floor
state: New York
Study officials:
affiliation: University at Buffalo
name: Paresh Dandona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghanim H, Abuaysheh S, Hejna J, Green K, Batra M, Makdissi A, Chaudhuri A, Dandona P. Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgaa057. doi: 10.1210/clinem/dgaa057.