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

NCT01003236 | Completed Phase 2 DMC

• 1 other identifier: 4774
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Diabetic nephropathy; Type II Diabetes; Milk Thistle extract; Silymarin

Outcome Measures

Primary Outcomes (1)

• Change from baseline in urinary albumin-creatinine ratio

  3 month

Secondary Outcomes (11)

• Change from baseline in urinary TNF-α

  3 month

• Change from baseline in urinary TGF-β

  3 month

• Change from baseline in fasting plasma glucose

  3 month

• Change from baseline in blood lipid profile

  3 month

• Change from baseline in hemoglobin A1C

  3 month

Study Arms (2)

placebo

PLACEBO COMPARATOR

1 tablet 3 times daily

Drug: placebo

Milk Thistle extract

EXPERIMENTAL

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

Drug: Milk Thistle extract

Interventions

placebo DRUG

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

placebo

Milk Thistle extract DRUG

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

Also known as: Livergol made by Goldaru Pharmaceutical Company (Iran)

Milk Thistle extract

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shiraz University of Medical Sciences: lead

Study Sites (1)

Motahari Clinic

Shiraz, Fars, 71345, Iran

Location

Related Publications (2)

• 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.

  PMID: 37916745 DERIVED

• 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.

  PMID: 22770926 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus, Type 2

Interventions

milk-thistle extract

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ghazal Vessal, PharmD, PhD

  Shiraz University of Medical Sciences, Faculty of Pharmacy

  STUDY DIRECTOR

• Mohammad Mehdi Sagheb, MD

  Shiraz University of Medical Sciences

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: October 27, 2009
• First Posted: October 28, 2009
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: November 1, 2011
• Last Updated: June 25, 2012

Record last verified: 2012-06

Locations

IR (1)