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

Diabetic Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01003236
• Other study ID #: 4774
• Status: Completed
• Phase: Phase 2
• First received: October 27, 2009
• Last updated: June 21, 2012
• Start date: October 2010
• Est. completion date: November 2011

Study information

• Verified date: June 2012
• Source: Shiraz University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

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

Locations

Country	Name	City	State
Iran, Islamic Republic of	Motahari Clinic	Shiraz	Fars

Sponsors (1)

Lead Sponsor	Collaborator
Shiraz University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in urinary albumin-creatinine ratio		3 month	No
Secondary	Change from baseline in urinary TNF-a		3 month	No
Secondary	Change from baseline in urinary TGF-ß		3 month	No
Secondary	Change from baseline in fasting plasma glucose		3 month	No
Secondary	Change from baseline in blood lipid profile		3 month	No
Secondary	Change from baseline in hemoglobin A1C		3 month	No
Secondary	Change from baseline in urinary MDA		3 month	No
Secondary	Change from baseline in serum TNF-a		3 month	No
Secondary	Change from baseline in serum TGF-ß		3 month	No
Secondary	Change from baseline in serum MDA		3 month	No
Secondary	Change from baseline in estimated GFR		3 month	No
Secondary	Change from baseline in serum creatinine		3 month	No