TY - JOUR
T1 - 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
AU - Reutens, Anne T.
AU - Jandeleit-Dahm, Karin
AU - Thomas, Merlin
AU - Salim, Agus
AU - De Livera, Alysha M.
AU - Bach, Leon A.
AU - Colman, Peter G.
AU - Davis, Timothy M.E.
AU - Ekinci, Elif I.
AU - Fulcher, Greg
AU - Hamblin, Peter Shane
AU - Kotowicz, Mark A.
AU - MacIsaac, Richard J.
AU - Morbey, Claire
AU - Simmons, David
AU - Soldatos, Georgia
AU - Wittert, Gary
AU - Wu, Ted
AU - Cooper, Mark E.
AU - Shaw, Jonathan E.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - albuminuria
KW - diabetes
KW - diabetic nephropathies
UR - http://hdl.handle.net/1959.7/uws:56334
U2 - 10.1016/j.cct.2019.105892
DO - 10.1016/j.cct.2019.105892
M3 - Article
SN - 1559-2030
SN - 0197-2456
VL - 90
JO - Contemporary Clinical Trials
JF - Contemporary Clinical Trials
M1 - 105892
ER -