Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes
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|ClinicalTrials.gov Identifier: NCT02796170|
Recruitment Status : Recruiting
First Posted : June 10, 2016
Last Update Posted : September 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Hypertension||Drug: Dapagliflozin Drug: Sulfonylurea Drug: Placebo||Phase 4|
Clinical trials of two SGLT2 inhibitors, canagliflozin and dapagliflozin, have reported drops in systolic blood pressure of ~5 mmHg. Inappropriate activation of intrarenal renin-angiotensin system (RAS) is a major contributor to the increased arterial pressure and tissue injury including diabetic nephropathy. A key factor in the intrarenal RAS activation is stimulation of intrarenal angiotensinogen (AGT) which is the precursor of angiotensin peptides. From previous studies, it has been shown that high blood sugars in patients with type1 and type 2 diabetes mellitus is accompanied by elevated intrarenal AGT and urinary AGT levels. High glucose results in stimulation of AGT production. The high glucose levels augments intrarenal AGT levels in diabetes mellitus leading to the development of high blood pressure and diabetic nephropathy.
The investigators propose to conduct a single-center randomized, double blind, cross over study of the effect of Dapagliflozin over 6 weeks, followed by placebo over 6 weeks on the other treatment allocation (those getting placebo first will cross over to Dapagliflozin and vice versa). Treatment will be stratified according to the underlying presence or absence of hypertension.
- Type 2 diabetes with hypertension and on RAAS blocking drugs with stable blood pressure on therapy; n= 20
- Type 2 diabetes without hypertension and not on RAAS blocking drugs n=10
If unable to recruit 10 participants without hypertension the investigators will increase the number with hypertension for a total of 30. Stratification by hypertension status will remain and is important in understanding the effect of SGLT2 inhibition in patients not on BP lowering drugs.
In addition a Sulfonylurea (SU) arm will also be included - 10 participants who are on metformin and other background therapy (with the exclusion of SGLT-2 inhibitor and sulfonylurea) will be recruited. This will be an open-labeled arm. Participants will assessed at baseline. Participants will then receive usual care for 6 weeks. At the end of 6 weeks, participants will then undergo another assessment before being provided SU for 6 weeks. At the end of 6 weeks, participants will undergo assessment again. The aim is to determine whether any effects seen with Dapagliflozin are specific to that drug or related simply to improved glycemic control.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes|
|Actual Study Start Date :||March 2016|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||December 2019|
Active Comparator: Dapagliflozin
This arm will undergo either 6 weeks of Dapagloflozin then 6 weeks of placebo, or 6 weeks of placebo then 6 weeks of Dapagloflozin
5mg pill taken once daily
5mg pill taken once daily- placebo of Dapagliflozin
This arm will be open label, participants will receive usual care for 6 weeks, then be provided a sulfonylurea medication for 6 weeks.
Subjects may take any of the sulfonlyurea medications, titration will be done per standard of care.
- Change in blood pressure from baseline to 6 weeks [ Time Frame: baseline to 6 weeks ]Blood pressure will be measured at baseline with a 24 hour ambulatory blood pressure machine, and again after 6 weeks of treatment.
- Change in urinary AGT levels from baseline to 6 weeks [ Time Frame: baseline to 6 weeks ]Urinary AGT will be measure through the collection of 24 hour urine at baseline and again after 6 weeks of treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02796170
|Contact: Bonnie L Katalenich, MPHfirstname.lastname@example.org|
|Contact: Tina K Thethi, MD, MPHemail@example.com|
|United States, Louisiana|
|New Orleans, Louisiana, United States, 70112|
|Contact: Bonnie L Katalenich, MPH 504-988-6200 firstname.lastname@example.org|