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

Anne T. Reutens, Karin Jandeleit-Dahm, Merlin Thomas, Agus Salim, Alysha M. De Livera, Leon A. Bach, Peter G. Colman, Timothy M.E. Davis, Elif I. Ekinci, Greg Fulcher, Peter Shane Hamblin, Mark A. Kotowicz, Richard J. MacIsaac, Claire Morbey, David Simmons, Georgia Soldatos, Gary Wittert, Ted Wu, Mark E. Cooper, Jonathan E. Shaw

Research output: Contribution to journalArticleOtherpeer-review

26 Citations (Scopus)


Purpose: 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. Design: This is a multi-center, randomized, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 400 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. Primary outcome measures: Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR. Conclusion: This study is important because it may identify a new way of slowing renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.

Original languageEnglish
Article number105892
Number of pages8
JournalContemporary Clinical Trials
Publication statusPublished - Mar 2020


  • Albuminuria
  • Diabetic nephropathy
  • NADPH oxidase
  • Type 1 diabetes

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