Evaluating the Renoprotective Effect of Milk Thistle Extract on Patients With Type II Diabetic Nephropathy

Study Overview
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Brief Summary
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There is considerable evidence that increased blood glucose results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress in a variety of tissues. This may lead to the activation of stress-sensitive intracellular signaling pathways, causing cellular damage and late complications of diabetes including renal injury. Although the investigators understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. The flavonoid complex silymarin, an extract from the milk thistle, and its major pharmacological active component silibinin are free radical scavengers and potent membrane stabilizers by preventing lipid peroxidation. Furthermore, during early stages of diabetes, flavonoids minimize oxidative stress, and inflammation which represent important factors in the development of diabetic nephropathy. In this study the investigators plan to evaluate the renoprotective effect of milk thistle extract on type II diabetic patients with kidney disease.

Official Title
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Evaluating the Preventive Effect of Milk Thistle Extract (Silymarin) on Progression of Diabetic Nephropathy, a Randomized, Double-blind, Placebo-controlled Clinical Trial.

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: placebo
* Drug: Milk Thistle extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type II diabetes Overt proteinuria defined by urinary albumin excretion > 300 mg/24 hr in 2 consecutive determinations despite treatment with highest FDA recommended doses of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker for at least 6 months. Treatment of hyperglycemia with (but not limited to) an oral hypoglycemic agent or insulin (If a thiazolidinedione is used, stable dose for at least 6 months) Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins Presence of diabetic retinopathy Signing informed consent Exclusion Criteria: Type I diabetes Advanced chronic kidney disease defined by estimated GFR < 30 ml/min/1.73 m2 Severely uncontrolled diabetes defined by HbA1C > 10% Uncontrolled hypertension defined by SBP >160 mmHg or DBP >100 mmHg despite antihypertensive therapy Secondary forms of hypertension with defined etiology other than diabetes mellitus Other renal diseases History of solid organ transplantation Chronic Heart Failure with NYHA class III or IV Active infection Pregnancy Use of one of the following medications within 2 months prior to enrollment in the study: Non-steroidal anti-inflammatory agents Antioxidants supplements including: vitamin E, vitamin C, N-acetyl- cysteine (NAC), Pentoxyfilline, Lipoic acid, Fish-oil extracts (omega-3 fatty acids), Soy extracts (isoflavones), Green-tea preparations, Pomegranate extracts, Grape extracts Active malignancy Hepatitis virus or Human Immunodeficiency virus infections History of drug or alcohol dependency Cigarette smoking Psychiatric or neurological condition, preventing aware consent to the study and/or adherence to the study protocol

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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>1 tablet 3 times daily | Drug: placebo<br>* 140 mg placebo tablets, 3 times per day for 3 months<br>|
| Experimental: Milk Thistle extract<br>1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day | Drug: Milk Thistle extract<br>* 1 tablet equal to 140mg silymarin administered 3 times a day for 3 months<br>* Other names: Livergol made by Goldaru Pharmaceutical Company (Iran);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary albumin-creatinine ratio |  | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urinary TNF-α |  | 3 month | 
| Change from baseline in urinary TGF-β |  | 3 month | 
| Change from baseline in fasting plasma glucose |  | 3 month | 
| Change from baseline in blood lipid profile |  | 3 month | 
| Change from baseline in hemoglobin A1C |  | 3 month | 
| Change from baseline in urinary MDA |  | 3 month | 
| Change from baseline in serum TNF-α |  | 3 month | 
| Change from baseline in serum TGF-β |  | 3 month | 
| Change from baseline in serum MDA |  | 3 month | 
| Change from baseline in estimated GFR |  | 3 month | 
| Change from baseline in serum creatinine |  | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic nephropathy, Type II Diabetes, Milk Thistle extract, Silymarin