Renohemodynamic Effects of Combined empagliflOzin and LosARtan

Sponsor
Amsterdam UMC, location VUmc
Study ID
NCT04238702
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
35 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Empagliflozin 10 MG — DRUG
    Empagliflozin 10 MG 7 days intervention period
  • Losartan 50Mg Tab — DRUG
    Losartan 50 MG 7 days intervention period
  • Placebo — OTHER
    Placebo 7 days intervention period

Study Details

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.

Key Dates

Start date
Nov 4, 2020
Status verified
Oct 2021
Primary completion
Sep 27, 2021
Completion
Sep 27, 2021

Study Design

Enrollment
24 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Empagliflozin + Losartan
    Empagliflozin + Losartan
  • Experimental: Losartan + Placebo
    Losartan + Placebo
  • Experimental: Empagliflozin + Placebo
    Losartan + Placebo
  • Placebo Comparator: Placebo + Placebo
    Placebo + Placebo

Primary Outcome Measure

Glomerular Filtration Rate (GFR) [ Time Frame: 7 days ]

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