Effect of Montelukast on Kidney and Vascular Function in Type 1 Diabetes

Study Overview
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Brief Summary
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Kidney disease is a common problem among people with type 1 diabetes and can lead to disability, dialysis, and early death. Inflammation plays a key role in the development of kidney disease in type 1 diabetes and targeting leukotrienes, inflammatory chemicals the body releases in response to allergic reactions, may represent a promising therapy to slow the progression of diabetic kidney disease. The current proposal will investigate whether montelukast, a leukotriene blocker, lowers increased levels of protein in the urine (an early marker of diabetic kidney disease), and improves kidney and cardiovascular function in people with type 1 diabetes and kidney disease.

Official Title
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Effect of Montelukast on Kidney and Vascular Function in Type 1 Diabetes

Conditions
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Albuminuria

Intervention / Treatment
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* Drug: Montelukast
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Type 1 diabetes for at least 5 years Urine albumin to creatinine ratio 30-5000 mg/g on first morning void eGFR 30-89 ml/min/1.73m2 at time of screening Blood pressure <140/90 mm Hg prior to randomization Use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker with stable dose for 4 weeks BMI < 40 kg/m2 (FMDBA measurements can be inaccurate in severely obese patients). Stable anti-hypertensive regimen for at least one month prior to randomization Stable regimen of insulin delivery, i.e. automated insulin delivery (AID) system or multiple daily injections) 4 weeks prior to randomization Sedentary or recreationally active (≤2 days of vigorous aerobic exercise as vigorous exercise may affect vascular function measurements) Able to provide consent Exclusion Criteria: Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year Uncontrolled hypertension Factors judged to limit adherence to interventions Anticipated initiation of dialysis or kidney transplantation within 6 months 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 (higher risk of neuropsychiatric reaction) Penicillin allergy Iodine allergy Shellfish allergy Current use of phenobarbital, rifampin or carbamazepine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One capsule daily | Other: Placebo<br>* 1 capsule daily<br>|
| Experimental: Montelukast<br>One 10mg capsule daily | Drug: Montelukast<br>* 10mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Albuminuria | Change in albuminuria from baseline to 6 months | Baseline, 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 | Baseline, 6 months | 
| Change in Large Elastic Artery Stiffness | Change in aortic pulse wave velocity from baseline to 6 months | Baseline, 6 months |