SMART 2D: Study of Montelukast's Effects on Renal and Cardiovascular Health in Adolescents and Young Adults With Type 2 Diabetes

Adolescents and young adults (AYA) with type 2 diabetes (T2D) have a more severe phenotype than what is seen in youth-onset type 1 diabetes or adult-onset T2D including earlier kidney and cardiovascular disease complications; and prioritizing new treatments, either for standalone use or in combination with other therapies is critical. T2D triggers the release of proinflammatory mediators called cysteinyl leukotrienes leading to damage to the kidneys and blood vessels. This clinical trial will evaluate the effects of montelukast, a cysteinyl leukotriene inhibitor, on kidney and vascular function in AYA with T2D to help direct future diabetes care to limit diabetic kidney and cardiovascular disease complications.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Montelukast; Drug: Montelukast Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 14-24 years
• Tanner stage >2
• Diabetes onset <18 years of age and <10 years duration prior to study start
• HgbA1c <10%
• Blood pressure <130/80 mm Hg prior to randomization
• Stable anti-hypertensive regimen for at least one month prior to randomization
• BMI < 40 kg/m2
• If on SGLT2 inhibitor, ACEi/ARB or GLP-1RA, stable dose for 4 weeks
• Patient or guardian able to provide consent

Exclusion Criteria:

• T1D
• Episode of diabetic ketoacidosis or hyperosmolar hyperglycemia within 60 days
• Uncontrolled hypertension
• eGFR <30 ml/min/1.73m2
• Macroalbuminuria with urine albumin to creatinine ratio >300 mg/g
• Current participation in another research study
• Pregnancy or planning to become pregnant or currently breastfeeding
• Allergy to aspirin
• Severe hepatic impairment (Child-Pugh Class C)
• History of major psychiatric disorder
• Use of inhaled or systemic corticosteroids or long-acting beta agonists
• Iodine or shellfish allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Montelukast Placebo; one microcrystalline cellulose tablet daily
Experimental: Montelukast	Drug: Montelukast; montelukast 10 mg daily for patients aged 15 and older, 5 mg daily for patients aged 14

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in renal vascular resistance (RVR)	Change in RVR from baseline to 6 months. RVR is calculated as mean arterial pressure (MAP)/renal blood flow (RBF). MAP is measured using a blood pressure cuff and RBF is calculated using p-aminohippurate clearance (PAH clearance).	0 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brachial artery flow mediated dilation (FMD)	Change in FMD from baseline to 6 months, measured using high-resolution ultrasonography	0 and 6 months
Change in aortic pulse-wave velocity (PWV)	Change in PWV from baseline to 6 months, measured using a transcutaneous tonometer	0 and 6 months
Change in endovascular biopsy	Change in endovascular biopsy from baseline to 6 months. Venous endothelial cells will be collected from the intima of the vessel using 2 sterile J-wires advanced and retracted through an 18-gauge catheter, then will be incubated with monoclonal antibodies for Nf-KB.	0 and 6 months
Change in urinary sCD163		0 and 6 months
Change in urinary MCP-1		0 and 6 months
Change in plasma MCP-1		0 and 6 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; montelukast
• Other Study ID Numbers: 25-2690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No