An Intervention to Examine the Effect of Vitamin D on Urine Protein Levels in Type 2 Diabetes

Study Overview
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Brief Summary
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Diabetic kidney disease (nephropathy) develops in nearly 40% of patients with type 2 diabetes mellitus. Diabetic nephropathy is caused by damage to the small blood vessels in the kidneys due to uncontrolled blood sugar levels, which mean that the kidneys become less effective at filtering urine. This is associated with albuminuria (protein in the urine). Treatment with some drugs reduces the loss of albumin through the urine and delays disease progression. There is increasing evidence that vitamin D could also be important in management of diabetic kidney disease. The aim of this study is to investigate the efficacy and safety of a combined regimen of calcitriol (active vitamin D) and established drugs for diabetic kidney disease.

Detailed Description
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The investigators propose to test the efficacy and safety of a combined regimen of calcitriol and angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in type 2 diabetes subjects with albuminuria. In the proposed study, the bioactive form of vitamin D (calcitriol) is being used for its ability to synergize with ACEI or ARB and prevent renal disease progression. The study expands on preliminary studies demonstrating a reduction in proteinuria with vitamin D analogue treatment, in subjects with both diabetic as well as non-diabetic kidney disease.

Official Title
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Intervention Using Vitamin D for Elevated Urinary ALbumin in Diabetes (IDEAL-2)

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years and less than 80 years Diagnosis of T2DM requiring treatment with at least one oral hypoglycaemic medication or insulin 2.1. Subjects will be considered to have established T2DM if the diagnosis of diabetes has been made and the subjects were treated with insulin or an oral hypoglycaemic agent for at least 6 months after diagnosis 2.2. Subjects will be considered to have newly established T2DM if the diagnosis of diabetes was diagnosed with a fasting plasma glucose ≥ 7 mmol/L (126 mg/dL) or haemoglobin A1c is >6.5% in the past 6 months Documented albuminuria defined as a presence of albuminuria on two occasions in the last six months: 3.1. Albumin ≥ 30 mg/24 hour in a 24 hour urine collection, or 3.2. Albumin ≥ 20 μg/min in a short-time urine collection, or 3.3. Albumin ≥ 30 mg/L in a spot urine sample, or 3.4. A spot-urine albumin-creatinine ration (ACR) ≥ 30 mg/g creatinine (≥ 2.5 mg/mmol creatinine in men, ≥ 3.5 mg/mmol creatinine in women) Estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease (MDRD) equation of ≥ 25 mL/min/1.73 m2 Exclusion Criteria: If female, positive pregnancy test or planning pregnancy in the subsequent 12 months Pregnant Breastfeeding Corrected serum calcium ≥ 2.62 mmol/L Serum Potassium > 5.2 mmol/L if not on ACEI or ARB; Serum Potassium > 6.0 mmol/L if on ACEI or ARB 25-hydroxyvitamin D (25-OH Vit D) > 80 ng/mL PTH > 200 pg/mL Poorly controlled hypertension defined as systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg Systolic blood pressure (SBP) ≤ 110 mm Hg History of kidney stones History of severe chronic disease (e.g. chronic liver disease) Active malignancy Recent diagnosis of acute renal failure within 3 months of screening visit Likelihood of renal replacement therapy within 1 year

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Participants are treated with angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) AND active vitamin D (Calcitriol) 0.25 micrograms orally per day for 26 weeks. | Drug: Calcitriol<br>* Active vitamin D (Calcitriol) 0.25 micrograms<br>* Other names: Active Vitamin D;|
| No Intervention: Usual Care<br>Participants are treated with ACEI/ARB alone for 26 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary albumin creatinine ratio (ACR) measured biochemically | Urine albumin and creatinine will be measured biochemically and their ratio calculated | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour urine albumin (24h UA) excretion | 24-hour urine albumin (24h UA) excretion measured biochemically | 26 weeks | 
| Estimated glomerular filtration rate (eGFR) | Calculated using the Modification of Diet in Renal Disease (MDRD) equation | 26 weeks | 
| Blood pressure | Blood pressure measured using a digital sphygmomanometer | 26 weeks |