Intervention Using Vitamin D for Elevated Urinary Albumin Treated With Losartan in Diabetes (IDEAL)

Study Overview
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Brief Summary
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This study is a single center open-label randomized controlled trial designed to evaluate the efficacy of calcitriol plus losartan therapy in subjects with type II diabetes and macroalbuminuria.

Detailed Description
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The investigators propose to test the efficacy and safety of a combined regimen of calcitriol and losartan in subjects with type II diabetes (T2DM) with macroalbuminuria. Should the investigators study confirm the hypothesis that the proposed novel regimen is superior to the current practice of renin-angiotensin-aldosterone system blockade, the study would significantly advance the care of subjects with type II diabetes and kidney disease in Qatar and worldwide. In this regard it is worth noting that the prevalence of end stage renal disease in Qatar is 202 subjects per million population. This would translate into fewer subjects requiring dialysis or transplantation, an enormous benefit to individuals and society.

Official Title
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Kidney Disease in Type 2 Diabetes Mellitus: Biomarker Discovery and Novel Therapeutics

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Dietary Supplement: Calcitriol
* Drug: Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T2DM requiring treatment with at least one oral hypoglycemic medication or insulin Macroalbuminuria as defined as the presence of a UACR greater than 300 mg/gm creatinine (30 mg/mmol creatinine) on two occasions in the last six months Estimated eGFR of 30 to 90 mL/min/1.73 m2 Exclusion Criteria: Positive Pregnancy Test or planning pregnancy in the subsequent 18months (if female) Serum Calcium > 2.45 mmol/L (9.8 mg/dL) Serum Phosphorus > 1.78 mmol/L (5.5 mg/dL) Serum Potassium > 5.5 mmol/L (5 mEq/L) Parathyroid hormone < 20 pg/mL or > 500 pg/mL Hemoglobin A1C > 12% 25-OH Vit D > 50 ng/mL Poorly controlled hypertension defined as systolic blood pressure >= 180 mm Hg or diastolic blood pressure >= 110 mm Hg History of kidney stones History of severe disease like chronic liver disease Active malignancy Active granulomatous diseases like turburculosis and sarcoidosis Recent diagnosis of acute renal failure within 3 months of screening visit Likelihood of renal replacement therapy within 1 year History of parathyroidectomy Currently taking calcitriol or 1,25-dihydroxyvitamin D analog Currently taking calcitonin, bisphosphonates, cinacalcet, teriparatide, glucocorticoids or other drugs that may affect calcium or bone metabolism (subjects may be taking calcium containing phosphate binder or other phosphate binder. Subjects may also be taking stable dose of estrogen/progestin) History of osteoporosis or other bone disorder requiring calcitriol therapy History of allergic reaction to calcitriol, paracalcitol, hectoral, or other 1,25-dihydroxyvitamin D analogs History of allergic reaction to losartan or any other angiotensin receptor blocker therapy Evidence of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 21 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Losartan alone<br>In the losartan alone group, subjects are prescribed: losartan 50mg twice daily. | Drug: Losartan<br> <br> |
| Experimental: Losartan and Calcitriol<br>In the losartan plus calcitriol group, subjects are prescribed: losartan 50mg twice daily and calcitriol 0.25mcg daily. | Dietary Supplement: Calcitriol<br> <br> * Other names: 1,25-dihydroxyvitamin D3;Drug: Losartan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24h urine 24hr urine albuminuria | 24h urine albuminuria (log transformed) from baseline to 12 months post-randomization in the losartan plus calcitriol group compared to the losartan alone group. | 12 month |