A physician-initiated double-blind, randomised, placebo-controlled, phase 2 study evaluating the efficacy and safety of inhibition of NADPH oxidase with the first-in-class Nox-1/4 inhibitor, GKT137831, in adults with type 1 diabetes and persistently elevated urinary albumin excretion: protocol and statistical considerations.

2020-03

Reutens, Anne T

Jandeleit-Dahm, Karin

Thomas, Merlin

Bach, Leon A

Colman, Peter G

Davis, Timothy M E

D'Emden, Michael

Ekinci, Elif I

Fulcher, Greg

Hamblin, Peter Shane

Kotowicz, Mark A

MacIsaac, Richard J

Morbey, Claire

Simmons, David

Soldatos, Georgia

Wittert, Gary

Wu, Ted

Cooper, Mark E

Shaw, Jonathan E

Albuminuria

Diabetic nephropathy;

NADPH oxidase

Type 1 diabetes

Journal Article

0000-0003-2372-395X

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10.1016/j.cct.2019.105892

Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease. This study will evaluate the effect of GKT137831 in treating clinical diabetic kidney disease. This is a multi-center, randomised, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 200 mg BID for 48 weeks. The study will randomize 142 participants who have persistent albuminuria and estimated glomerular filtration rate (eGFR) at baseline of at least 40 ml/min/1.73m2. Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR. This study is important because it may identify a new way of halting renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.

link

Contemporary Clinical Trials 2020; 90: 105892

Contemporary Clinical Trials