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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01003236
Recruitment Status : Completed
First Posted : October 28, 2009
Last Update Posted : June 25, 2012
Information provided by (Responsible Party):
Ghazal Vessal, 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.

Condition or disease Intervention/treatment Phase
Diabetic Nephropathy Drug: placebo Drug: Milk Thistle extract Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluating the Preventive Effect of Milk Thistle Extract (Silymarin) on Progression of Diabetic Nephropathy, a Randomized, Double-blind, Placebo-controlled Clinical Trial.
Study Start Date : October 2010
Actual Primary Completion Date : October 2011
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine

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 Name: Livergol made by Goldaru Pharmaceutical Company (Iran)

Primary Outcome Measures :
  1. Change from baseline in urinary albumin-creatinine ratio [ Time Frame: 3 month ]

Secondary Outcome Measures :
  1. Change from baseline in urinary TNF-α [ Time Frame: 3 month ]
  2. Change from baseline in urinary TGF-β [ Time Frame: 3 month ]
  3. Change from baseline in fasting plasma glucose [ Time Frame: 3 month ]
  4. Change from baseline in blood lipid profile [ Time Frame: 3 month ]
  5. Change from baseline in hemoglobin A1C [ Time Frame: 3 month ]
  6. Change from baseline in urinary MDA [ Time Frame: 3 month ]
  7. Change from baseline in serum TNF-α [ Time Frame: 3 month ]
  8. Change from baseline in serum TGF-β [ Time Frame: 3 month ]
  9. Change from baseline in serum MDA [ Time Frame: 3 month ]
  10. Change from baseline in estimated GFR [ Time Frame: 3 month ]
  11. Change from baseline in serum creatinine [ Time Frame: 3 month ]

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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01003236

Iran, Islamic Republic of
Motahari Clinic
Shiraz, Fars, Iran, Islamic Republic of, 71345
Sponsors and Collaborators
Shiraz University of Medical Sciences
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 automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Ghazal Vessal, Dr, Shiraz University of Medical Sciences Identifier: NCT01003236     History of Changes
Other Study ID Numbers: 4774
First Posted: October 28, 2009    Key Record Dates
Last Update Posted: June 25, 2012
Last Verified: June 2012

Keywords provided by Ghazal Vessal, Shiraz University of Medical Sciences:
Diabetic nephropathy
Type II Diabetes
Milk Thistle extract

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs