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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2011

Interventions

  • Drug: placebo
    • 140 mg placebo tablets, 3 times per day for 3 months
  • Drug: Milk Thistle extract
    • 1 tablet equal to 140mg silymarin administered 3 times a day for 3 months

Arms, Groups and Cohorts

  • Placebo Comparator: placebo
    • 1 tablet 3 times daily
  • Experimental: Milk Thistle extract
    • 1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day

Clinical Trial Outcome Measures

Primary Measures

  • Change from baseline in urinary albumin-creatinine ratio
    • Time Frame: 3 month

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 30 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Shiraz University of Medical Sciences
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ghazal Vessal, Dr – Shiraz University of Medical Sciences
  • Overall Official(s)
    • Ghazal Vessal, PharmD, PhD, Study Director, Shiraz University of Medical Sciences, Faculty of Pharmacy
    • Mohammad Mehdi Sagheb, MD, Study Chair, Shiraz University of Medical Sciences
    • Jamshid Roozbeh, MD, Principal Investigator, Shiraz University of Medical Sciences, Nephrology Urology Research Center
    • Mohammad Kazem Fallahzadeh Abarghouei, M.D., Principal Investigator, Shiraz University of Medical Sciences

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