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Renohemodynamic Effects of Combined empagliflOzin and LosARtan

NCT04238702 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2021-10-08

No results posted yet for this study

Summary

Worldwide, diabetic kidney disease (DKD) is the most common cause of chronic and end stage kidney disease. In parallel with the ever-increasing rates of obesity and type 2 diabetes (T2D), the incidence of DKD is expected to further increase in the coming years. DKD is a multi-factorial condition, involving pathophysiological factors such as chronic hyperglycemia, obesity, systemic- and glomerular hypertension, dyslipidemia, oxidative stress and pro-inflammatory cytokines. Large-sized prospective randomized clinical trials indicate that intensified glucose and blood pressure control, the latter especially by using agents that interfere with the renin-angiotensin-aldosterone system (RAS), halts the onset and (particularly) the progression of DKD, in both type 1 diabetes mellitus (T1DM) and T2DM patients. However, despite the wide use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), a considerable amount of patients develop DKD, indicating an unmet need for renoprotective therapies. Sodium-glucose linked transporters (SGLT-2) inhibitors are a relatively novel glucose-lowering drug for the treatment of T2DM. These agents seem to exert pleiotropic actions 'beyond glucose control'. SGLT-2 inhibitors decrease proximal sodium reabsorption and decrease glomerular pressure and albuminuria in type 2 diabetes. In addition, SGLT-2 inhibitors reduce blood pressure and body weight. At this point in time, the renoprotective mechanisms involved with SGLT-2 inhibition still remain speculative, though a consistent finding is that SGLT-2 inhibitors reduce estimated eGFR after first dosing, which is reversible after treatment cessation. This "dip" indicates a renal hemodynamic phenomenon reminiscent of the RAS blockers and is thought to reflect a reduction in intraglomerular pressure. The potential renoprotective effects and mechanisms of combination therapy of SGLT-2 inhibitors and RAS inhibitors have not been sufficiently detailed in human type 2 diabetes. Therefore, the current study aims to explore the underlying mechanism of the improved renal hemodynamics and mechanistics of mono- and combination therapy with an SGLT-2 inhibitor and a RAS inhibitor on renal physiology in metformin and/or SU-treated T2DM patients.

Conditions

  • Diabetes Mellitus, Type 2
  • Diabetic Kidney Disease

Interventions

DRUG

Empagliflozin 10 MG

Empagliflozin 10 MG 7 days intervention period

DRUG

Losartan 50Mg Tab

Losartan 50 MG 7 days intervention period

OTHER

Placebo

Placebo 7 days intervention period

Sponsors & Collaborators

  • Amsterdam UMC, location VUmc

    lead OTHER

Principal Investigators

  • Daniel van Raalte, MD PhD · Amsterdam UMC, location VU Medical Center

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
CROSSOVER

Eligibility

Min Age
35 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-11-04
Primary Completion
2021-09-27
Completion
2021-09-27

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04238702 on ClinicalTrials.gov