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

Phase 2

Completed

• Conditions: Diabetic Nephropathy
• Interventions: Drug: placebo; Drug: Milk Thistle extract

• Registration Number: NCT01003236
• Lead Sponsor: Shiraz University of Medical Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-10-27
• Study First Submitted QC: 2009-10-27
• Study First Posted: 2009-10-28
• Study Start: 2010-10
• Primary Completion: 2011-10
• Study Completion: 2011-11
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-21
• Last Update Posted: 2012-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	1 tablet 3 times daily
Milk Thistle extract	Milk Thistle extract	1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day

Primary Outcome Measures

Name	Time	Method
Change from baseline in urinary albumin-creatinine ratio	3 month

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Motahari Clinic; 🇮🇷 Shiraz, Fars, Iran, Islamic Republic of