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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: placebo; Drug: Milk Thistle extract

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of, 71345
      • Motahari Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; 1 tablet 3 times daily	Drug: placebo; 140 mg placebo tablets, 3 times per day for 3 months
Experimental: Milk Thistle extract; 1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day	Drug: Milk Thistle extract; 1 tablet equal to 140mg silymarin administered 3 times a day for 3 months; Other Names: Livergol made by Goldaru Pharmaceutical Company (Iran)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shiraz University of Medical Sciences
• Investigators: Study Director: Ghazal Vessal, PharmD, PhD, Shiraz University of Medical Sciences, Faculty of Pharmacy; Study Chair: Mohammad Mehdi Sagheb, MD, shiraz University of medical sciences; Principal Investigator: Jamshid Roozbeh, MD, Shiraz University of Medical Sciences, Nephrology Urology Research Center; Principal Investigator: Mohammad Kazem Fallahzadeh Abarghouei, M.D., shiraz University of medical sciences

Publications and helpful links

General Publications

• Fallahzadeh MK, Dormanesh B, Sagheb MM, Roozbeh J, Vessal G, Pakfetrat M, Daneshbod Y, Kamali-Sarvestani E, Lankarani KB. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial. Am J Kidney Dis. 2012 Dec;60(6):896-903. doi: 10.1053/j.ajkd.2012.06.005. Epub 2012 Jul 7.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: October 27, 2009
• First Submitted That Met QC Criteria: October 27, 2009
• First Posted (Estimate): October 28, 2009

Study Record Updates

• Last Update Posted (Estimate): June 25, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Type II Diabetes; Silymarin; Diabetic nephropathy; Milk Thistle extract
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: 4774