Diabetic Nephropathies
Conditions
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTCalcitriol
DRUGLosartan
Sponsors
Hamad Medical Corporation
Weill Medical College of Cornell University
Weill Cornell Medical College in Qatar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of T2DM requiring treatment with at least one oral hypoglycemic medication or insulin 2. 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 3. Estimated eGFR of 30 to 90 mL/min/1.73 m2
Exclusion criteria
1. Positive Pregnancy Test or planning pregnancy in the subsequent 18months (if female) 2. Serum Calcium \> 2.45 mmol/L (9.8 mg/dL) 3. Serum Phosphorus \> 1.78 mmol/L (5.5 mg/dL) 4. Serum Potassium \> 5.5 mmol/L (5 mEq/L) 5. Parathyroid hormone \< 20 pg/mL or \> 500 pg/mL 6. Hemoglobin A1C \> 12% 7. 25-OH Vit D \> 50 ng/mL 8. Poorly controlled hypertension defined as systolic blood pressure \>= 180 mm Hg or diastolic blood pressure \>= 110 mm Hg 9. History of kidney stones 10. History of severe disease like chronic liver disease 11. Active malignancy 12. Active granulomatous diseases like turburculosis and sarcoidosis 13. Recent diagnosis of acute renal failure within 3 months of screening visit 14. Likelihood of renal replacement therapy within 1 year 15. History of parathyroidectomy 16. Currently taking calcitriol or 1,25-dihydroxyvitamin D analog 17. 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) 18. History of osteoporosis or other bone disorder requiring calcitriol therapy 19. History of allergic reaction to calcitriol, paracalcitol, hectoral, or other 1,25-dihydroxyvitamin D analogs 20. History of allergic reaction to losartan or any other angiotensin receptor blocker therapy 21. Evidence of drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24h urine 24hr urine albuminuria | 12 month | 24h urine albuminuria (log transformed) from baseline to 12 months post-randomization in the losartan plus calcitriol group compared to the losartan alone group. |
Other
| Measure | Time frame |
|---|---|
| Urine mRNA/miRNA expression | 15 months |
| Urine Albumin-to-Creatinine Ratio (UACR) | 15 months |
| Blood Pressure (BP) | 15 months |
| Estimated glomuerula filtration rate (eGFR) | 15 months |
Countries
Qatar, United States
Outcome results
None listed