Clinical trial NCT01003236: Evaluating the Renoprotective Effect of Milk Thistle Extract on Patients With Type II Diabetic Nephropathy
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Keywords: Diabetic nephropathy
Type II Diabetes
Milk Thistle extract
Silymarin
Lead sponsor: Shiraz University of Medical Sciences
Sponsor class: OTHER
First posted: 2009-10-28
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change from baseline in urinary albumin-creatinine ratio
timeFrame: 3 month
Secondary outcomes:
measure: Change from baseline in urinary TNF-α
timeFrame: 3 month
measure: Change from baseline in urinary TGF-β
timeFrame: 3 month
measure: Change from baseline in fasting plasma glucose
timeFrame: 3 month
measure: Change from baseline in blood lipid profile
timeFrame: 3 month
measure: Change from baseline in hemoglobin A1C
timeFrame: 3 month
measure: Change from baseline in urinary MDA
timeFrame: 3 month
measure: Change from baseline in serum TNF-α
timeFrame: 3 month
measure: Change from baseline in serum TGF-β
timeFrame: 3 month
measure: Change from baseline in serum MDA
timeFrame: 3 month
measure: Change from baseline in estimated GFR
timeFrame: 3 month
measure: Change from baseline in serum creatinine
timeFrame: 3 month
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Motahari Clinic
state: Fars
Study officials:
affiliation: Shiraz University of Medical Sciences, Faculty of Pharmacy
name: Ghazal Vessal, PharmD, PhD
role: STUDY_DIRECTOR
affiliation: Shiraz University of Medical Sciences
name: Mohammad Mehdi Sagheb, MD
role: STUDY_CHAIR
affiliation: Shiraz University of Medical Sciences, Nephrology Urology Research Center
name: Jamshid Roozbeh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shiraz University of Medical Sciences
name: Mohammad Kazem Fallahzadeh Abarghouei, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.