Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes

Award Number: R01DK145012
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/14/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

Group Awards By:

View Award Description

MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes - PROJECT SUMMARY/ABSTRACT Diabetes is accompanied by significant morbidity and mortality due to microvascular and macrovascular complications. Progression of diabetic kidney disease (DKD) to end stage kidney disease impairs patients’ quality of life and results in high rates of cardiovascular disease (CVD) and premature deaths. Diabetic retinopathy, which correlates strongly with nephropathy, remains the leading cause of blindness. The pathogenic events that drive kidney, vascular and retinal disease progression include chronic inflammation, vascular permeability, tubular epithelial atrophy, and fibrosis. Our early studies have shown that macrophages exacerbate kidney damage and fibrosis through activation of the 5-lipooxygenase (5-LO) pathway. This pathway orchestrates the synthesis of proinflammatory lipid mediators, termed leukotrienes, which have been implicated in the pathogenesis of DKD, retinopathy and CVD. Our work reveals that leukotrienes foster chronic inflammation and maladaptive renal tubular repair in numerous mouse models of renal fibrosis. We have found that short-term inhibition of cysteinyl leukotrienes with montelukast (a cysteinyl leukotriene receptor antagonist) in mice with acute kidney injury robustly prevents chronic kidney disease. In a type 1 diabetes mouse model, we found that montelukast inhibits early diabetic retinopathy. In a large cohort of patients, we show that montelukast use is associated with significantly lower risk of kidney failure and with lower systolic blood pressure. Our preliminary data also suggests that montelukast reduces albuminuria and arterial stiffness and improves vascular endothelial function in patients with type 1 diabetes. We have found that montelukast attenuates arterial stiffness in mice. Finally, we show that leukotriene pathways are elevated in patients with type 2 diabetes (T2D) suggesting this population may benefit from leukotriene inhibition. To date, no interventional studies have examined the effect of montelukast on kidney, vascular or retinal outcomes in patients with T2D. We propose a 12-month, randomized, double-blind, placebo-controlled study in 110 adult participants with T2D with CKD stage 2-3 (eGFR 30-89 ml/min/1.73m2) and albuminuria (urine albumin to creatinine ratio of 30-5000 mg/g) to examine the effect of montelukast vs. placebo on kidney, vascular and retinal function. The primary outcome is change in albuminuria. In Aim 1, we will determine the effect of 12 months of montelukast vs. placebo on 24-hour albuminuria (primary outcome) and glomerular filtration rate. In Aim 2, we will determine the effect of 12 months of montelukast vs. placebo on vascular endothelial function and arterial stiffness assessed by brachial artery flow-mediated dilation and aortic pulse wave velocity. In our exploratory Aim 3, we will assess the 12-month impact of montelukast vs. placebo on diabetic retinopathy measured by optical coherence tomographic angiography (OCTA)). The expected results will provide the necessary information to support an outcomes trial that could establish montelukast as a safe, well-tolerated therapy for improving microvascular and macrovascular diabetes complications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $737,870 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/18/2026	NEW	$737,870
														Subtotal = $737,870

Grand Total All Awards = $737,870

Top

All Categories

About

Search

Reports

Data Submission

Award Information

MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes

Award Number: R01DK145012

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/14/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer