Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes

NCT02796170 | Completed Phase 4 Results

• 1 other identifier: 812701
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on blood pressure and urinary angiotensinogen. This is a cross over study design, where 40 subjects will receive Dapagliflozin for 6 weeks followed by placebo for 6 weeks, or placebo for 6 weeks followed by Dapagliflozin for 6 weeks. In addition there will be an arm of 10 subjects who will receive sulfonylurea in an open label as a comparative to the cross over subjects to assess if the effect of Dapagliflozin may also be in part due to improved glycemic control.

Conditions

Type 2 Diabetes; Hypertension

Keywords

SGLT-2 inhibitor; urinary angiotensinogen

Outcome Measures

Primary Outcomes (1)

• Change in Blood Pressure From Baseline to 6 Weeks Measured by ABPM

  Blood pressure was measured at baseline with a 24 hour ambulatory blood pressure machine (ABPM), and again after 6 weeks of treatment.

  Baseline to 6 weeks

Secondary Outcomes (1)

• Change in Urinary AGT Levels From Baseline to 6 Weeks

  Baseline to 6 weeks

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

Participants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin.

Drug: Dapagliflozin; Drug: Placebo

Placebo

ACTIVE COMPARATOR

Participants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin.

Drug: Dapagliflozin; Drug: Placebo

Interventions

Dapagliflozin DRUG

5mg pill taken once daily

Dapagliflozin; Placebo

Placebo DRUG

5mg pill taken once daily- placebo of Dapagliflozin

Dapagliflozin; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes with hypertension and on RAAS blocking drugs OR
• Type 2 diabetes without hypertension and not on RAAS blocking drugs
• Hemoglobin A1c between 7% and 9% (inclusive)
• Estimated glomerular filtration rate (eGFR) ≥60 ml/min
• Capacity to understand and sign informed consent

You may not qualify if:

• Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>3x upper limit of normal (ULN)
• Total bilirubin \>2.0 mg/dL
• Positive serologic evidence of current infectious liver disease, including Hepatitis B viral antibody immunoglobulin M (IGM), Hepatitis B surface antigen, and Hepatitis C virus antibody
• Estimated glomerular filtration rate (eGFR) \<60 ml/min
• Recent cardiovascular events with the last 2 months: acute coronary syndrome (ACS), hospitalization for unstable angina or acute myocardial infarction, acute stroke or transient ischemic attack (TIA), or post coronary artery revascularization
• Congestive Heart Failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure
• Pregnant or breastfeeding patients
• Patients who, in the judgement of the investigator, may be at risk for dehydration
• Blood pressure at enrollment: Systolic ≥165 mmHg and/or Diastolic ≥110 mmHg; At randomization: Systolic ≥160 mmHg and/or Diastolic ≥100 mmHg

Sponsors & Collaborators

• Tulane University School of Medicine: lead
• AstraZeneca: collaborator

Study Sites (1)

Tulane University

New Orleans, Louisiana, 70112, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dragana Lovre
• Organization: Tulane University

dlovre@tulane.edu

(504)988-9928

Study Officials

• Dragana Lovre, MD

  Tulane University School of Medicine

  PRINCIPAL INVESTIGATOR

• Tina Thethi, MD

  AdventHealth

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: June 10, 2016
• Study Start: March 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2020
• Last Updated: November 1, 2022
• Results First Posted: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)