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

NCT ID: NCT01003236

Last Updated: 2012-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2011-11-30

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.

Conditions

Diabetic Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

placebo

1 tablet 3 times daily

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

140 mg placebo tablets, 3 times per day for 3 months

Milk Thistle extract

1 tablet of the extract (equivalent to 140 mg silymarin) 3 times per day

Group Type: EXPERIMENTAL

Milk Thistle extract

Intervention Type: DRUG

1 tablet equal to 140mg silymarin administered 3 times a day for 3 months

Interventions

placebo

140 mg placebo tablets, 3 times per day for 3 months

Intervention Type: DRUG

Milk Thistle extract

1 tablet equal to 140mg silymarin administered 3 times a day for 3 months

Intervention Type: DRUG

Other Intervention Names

Livergol made by Goldaru Pharmaceutical Company (Iran)

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shiraz University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Ghazal Vessal

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ghazal Vessal, PharmD, PhD

Role: STUDY_DIRECTOR

Shiraz University of Medical Sciences, Faculty of Pharmacy

Mohammad Mehdi Sagheb, MD

Role: STUDY_CHAIR

Shiraz University of Medical Sciences

Jamshid Roozbeh, MD

Role: PRINCIPAL_INVESTIGATOR

Shiraz University of Medical Sciences, Nephrology Urology Research Center

Mohammad Kazem Fallahzadeh Abarghouei, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shiraz University of Medical Sciences

Locations

Motahari Clinic

Shiraz, Fars, Iran

Countries

Iran

References

Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.

Reference Type: DERIVED

PMID: 37916745 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22770926 (View on PubMed)

Other Identifiers

4774

Identifier Type: -

Identifier Source: org_study_id