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

NCT ID: NCT02433678

Last Updated: 2019-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2018-11-30

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Patients will be treated for 12 weeks with placebo once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Dapagliflozin

10 mg daily for the 12 weeks

Group Type: ACTIVE_COMPARATOR

dapagliflozin

Intervention Type: DRUG

SGLT-2 inhibitor for the treatment of type 2 diabetes

Interventions

dapagliflozin

SGLT-2 inhibitor for the treatment of type 2 diabetes

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Farxiga

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaleida Health

OTHER

Sponsor Role: collaborator

University at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Paresh Dandona

distinguished professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paresh Dandona, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University at Buffalo

Locations

ECMC Ambulatory Center, 3rd Floor

Buffalo, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32044999 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

1972

Identifier Type: -

Identifier Source: org_study_id