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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ghazal Vessal, Shiraz University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01003236
First received: October 27, 2009
Last updated: June 21, 2012
Last verified: June 2012
History of Changes
  Purpose

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 Intervention Phase
Diabetic Nephropathy
 Drug: placebo
Drug: Milk Thistle extract
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Shiraz University of Medical Sciences:

Primary Outcome Measures:
  • Change from baseline in urinary albumin-creatinine ratio [ Time Frame: 3 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in urinary TNF-α [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in urinary TGF-β [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in blood lipid profile [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in hemoglobin A1C [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in urinary MDA [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in serum TNF-α [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in serum TGF-β [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in serum MDA [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in estimated GFR [ Time Frame: 3 month ] [ Designated as safety issue: No ]
  • Change from baseline in serum creatinine [ Time Frame: 3 month ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: October 2010
Study Completion Date: November 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01003236

Locations
Iran, Islamic Republic of
Motahari Clinic
Shiraz, Fars, Iran, Islamic Republic of, 71345
Sponsors and Collaborators
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
  More Information

No publications provided by Shiraz University of Medical Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Ghazal Vessal, Dr, Shiraz University of Medical Sciences
ClinicalTrials.gov Identifier: NCT01003236     History of Changes
Other Study ID Numbers: 4774
Study First Received: October 27, 2009
Last Updated: June 21, 2012
Health Authority: Iran: Ethics Committee

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

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

ClinicalTrials.gov processed this record on May 23, 2013