Add-on Pentoxifylline to Losartan Versus Increasing Dose of Losartan on NT-PRO BNP in Type 2 Diabetics With Nephropathy

Study Overview
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Brief Summary
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This study was designed to assess the efficacy of adding pentoxifylline to losartan in comparison with increasing dose of losartan in type 2 diabetes patients with nephropathy. also the effect of pentoxifylline on N terminal brain natriuretic peptide (NT-pro BNP) and C-reactive protein

Detailed Description
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Addition of pentoxifylline to losartan provides antiproteinuric effects in type 2 diabetes patients with nephropathy that might relate to its effect on N terminal brain natriuretic peptide (NT-pro BNP) and C-reactive protein. Pentoxifylline is a phosphodiestrase inhibitor with anti-inflammatory effects that was used in type 2 diabetes patients with nephropathy for treatment of diabetes complications. NT-Pro BNP, which is released from the heart due to wall stress and pressures, is known as a diagnostic and prognostic marker for heart failure and cardiovascular mortality in type 2 diabetes.

Official Title
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Comparative Effects of add-on Pentoxifylline to Losartan Versus Increasing Dose of Losartan on Serum NT-PRO BNP and Proteinuria in Type 2 Diabetics With Nephropathy

Conditions
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Diabetic Nephropathies

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Losartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age>30 and age<70, urinary albumin excretion (UAE) ≥150 mg/24 h Exclusion Criteria: any infectious or malignant diseases, non-diabetic kidney disease, retinal hemorrhage, acute myocardial infarction, uncontrolled hypertension, pregnancy, unable to follow up, hyperthyroidism, baseline serum potassium concentrations ≥5.5 meq/L, glomerular filtration rate (GFR)<30mL/min/1.73 m and intolerance of pentoxifylline

Ages Eligible for Study
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Minimum Age: 38 Years
Maximum Age: 76 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pentoxifylline & losartan<br>pentoxifylline arm took 400 mg pentoxifylline twice daily plus 50mg losartan daily for 12 weeks. | Drug: Pentoxifylline<br>* pentoxifylline arm took 400 mg pentoxifylline twice daily plus 50mg losartan daily for 12 weeks.<br>* Other names: oxpentifylline;Drug: Losartan<br>* losartan arm took 100mg losartan daily for 12 weeks.<br>* Other names: Cozaar;|
| Active Comparator: Losartan<br>losartan arm took 100mg losartan daily for 12 weeks. | Drug: Losartan<br>* losartan arm took 100mg losartan daily for 12 weeks.<br>* Other names: Cozaar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| N terminal brain natriuretic peptide (NT-pro BNP) | N terminal brain natriuretic peptide assessed using ELISA method (zelbio, Germany) with inter- and intra-assay coefficient of variation (CV) <12% and <10%. Measured at baseline, 3rd month | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Highly sensitive C-reactive protein (hsCRP) | Highly sensitive C-reactive protein assessed by commercial kits (DRG kit, Germany) using the ELISA (enzyme-linked immunosorbent assay) method with inter- and intra-assay coefficient of variation (CV) of <20%. Measured at baseline, 3rd month | 3 months | 
| Urinary albumin excretion | Urinary albumin excretion assessed by overnight (12 hour) collection of urine. Measured at baseline, 3rd month | 3 months | 
| Blood pressure | Systolic and diastolic blood pressure assessed by mercury sphygnomanometry. Patients were placed in a sitting position and after ten minutes rest, two readings from right-side hand with five minutes interval were obtained. Measured at baseline, 3rd month | 3 months | 
| estimated glomerular filtration rate | estimated glomerular filtration rate calculated using the formula developed by Chronic Kidney Disease Epidemiology Collaboration. Measured at baseline, 3rd month | 3 months | 
| serum creatinine concentrations | serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month | 3 months |