Type 2 Diabetes
Conditions
Keywords
montelukast, diabetes, type two diabetes, kidney function, blood vessel function, inflammation, smart2d
Brief summary
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.
Interventions
DRUGMontelukast
montelukast 10 mg daily for patients aged 15 and older, 5 mg daily for patients aged 14
one microcrystalline cellulose tablet daily
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to 24 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in renal vascular resistance (RVR) | 0 and 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brachial artery flow mediated dilation (FMD) | 0 and 6 months | Change in FMD from baseline to 6 months, measured using high-resolution ultrasonography |
| Change in aortic pulse-wave velocity (PWV) | 0 and 6 months | Change in PWV from baseline to 6 months, measured using a transcutaneous tonometer |
| Change in endovascular biopsy | 0 and 6 months | 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. |
| 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 | — |
Countries
United States
Outcome results
None listed