N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy

NCT01265563 | Completed Phase 2 Results DMC

• 3 other identifiers: CLIN-004-10S1R21AT004490-01A1VA 1I01CX000264-01A2
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The study is done to find out whether the combined use of the nutritional supplements N-acetylcysteine and Siliphos (milk thistle extract) corrects the shedding of urine protein and oxidative damage (damage to cells and organs often compared to fast aging) in patients with Type 2 Diabetes Mellitus (T2DM) and diabetic kidney disease.

Conditions

Diabetic Nephropathy; Proteinuria; Oxidative Stress

Keywords

silymarin; glutathione; diabetic nephropathies; oxidative stress; N-acetylcysteine; protein tholation

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Urinary Albumin Excretion

  Urine albumin to creatinine ratio was assessed at the end of run in period and after 3 months administration of study intervention.

  Baseline and 3 months

Secondary Outcomes (2)

• Change From Baseline in Hemoglobin-A1c

  Baseline and 3 months

• Urinary Alpha-1 Microglobulin, Inflammatory Cytokines and C-C Chemokines

  Baseline and 3 months

Study Arms (5)

NAC placebo and Silibin placebo

PLACEBO COMPARATOR

Drug: N-acetylcysteine placebo and Drug: Silibin placebo

Drug: N-acetylcysteine placebo and silibin placebo

NAC active and Silibin placebo

EXPERIMENTAL

Drug: N-acetylcysteine and Drug: Silibin placebo

Drug: N-acetylcysteine active and silibin placebo

NAC placebo and Silibin active

EXPERIMENTAL

Drug: N-acetylcysteine placebo and Drug: Silibin active

Drug: N-acetylcysteine placebo and silibin active

NAC active and Silibin active

EXPERIMENTAL

Drug: N-acetylcysteine active and Drug: Silibin active

Drug: N-acetylcysteine active and silibin active

NAC active and High-dose Silibin active

EXPERIMENTAL

Drug: N-acetylcysteine active and Drug: Silibin higher dose active

Drug: N-acetylcysteine active + high-dose silibin active

Interventions

N-acetylcysteine placebo and silibin placebo DRUG

Dietary Supplement: N-acetylcysteine placebo excipient and silibin placebo orally twice daily for three months

Also known as: NAC placebo, Silibin-phosphatidylcholine placebo, Siliphos placebo

NAC placebo and Silibin placebo

N-acetylcysteine active and silibin placebo DRUG

Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin placebo orally twice a day for three months

Also known as: NAC, Silibin-phosphatidylcholine placebo, Siliphos placebo

NAC active and Silibin placebo

N-acetylcysteine placebo and silibin active DRUG

Dietary Supplement: silibin 480 mg orally twice daily and N-acetylcysteine placebo orally twice a day for three months

Also known as: NAC Placebo, Silibin-phosphatidylcholine, Siliphos

NAC placebo and Silibin active

N-acetylcysteine active and silibin active DRUG

Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 480 mg orally twice daily for three months

Also known as: NAC, Silibin-phosphatidylcholine, Siliphos

NAC active and Silibin active

N-acetylcysteine active + high-dose silibin active DRUG

Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 960 mg orally twice daily for three months

Also known as: NAC, Silibin-phosphatidylcholine, Siliphos

NAC active and High-dose Silibin active

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females age 18-76 years old
• Type 2 diabetes mellitus
• Diabetic nephropathy, as defined by:
• estimated GFR between 60 and 15 ml/min
• presence of proteinuria
• Current medical treatment with low dose aspirin
• Treatment of hypertension with (but not limited to):
• one diuretic
• one beta-blocker
• and one medication from the classes Angiotensin Receptor Blockers (ARBs) or Angiotensin Converting Enzyme inhibitors (ACE-I)
• Treatment of hyperglycemia with (but not limited to) glipizide and the medication class insulin
• Treatment of hypercholesterolemia with (but not limited to) one medication from the class statins

You may not qualify if:

• Type 1 diabetes mellitus
• Glycosylated hemoglobin (HbA1C) \> 10%
• \>20% variation in estimated GFR, during last 6 months
• Systolic Blood Pressure \>170 mmHg or Diastolic Blood Pressure \>100 mmHg on medications
• Other secondary forms of hypertension (endocrine, renovascular)
• History of intolerance to:
• Both ACE-I and ARBs
• The investigational supplements
• Iodinated radiologic contrast material
• Known non diabetic renal disease
• or history of solid organ transplantation
• Hepatitis virus or Human Immunodeficiency virus infections
• Use of one of the following medications within 2 months prior to enrollment in the study:
• Metformin
• Thiazolidinediones (pioglitazone or rosiglitazone)

Sponsors & Collaborators

• VA Office of Research and Development: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229, United States

Location

Related Publications (7)

• Debnath S, Thameem F, Alves T, Nolen J, Al-Shahrouri H, Bansal S, Abboud HE, Fanti P. Diabetic nephropathy among Mexican Americans. Clin Nephrol. 2012 Apr;77(4):332-44. doi: 10.5414/cn107487.

  PMID: 22445478 BACKGROUND

• Giustarini D, Dalle-Donne I, Milzani A, Fanti P, Rossi R. Analysis of GSH and GSSG after derivatization with N-ethylmaleimide. Nat Protoc. 2013 Sep;8(9):1660-9. doi: 10.1038/nprot.2013.095. Epub 2013 Aug 1.

  PMID: 23928499 BACKGROUND

• Khazim K, Giustarini D, Rossi R, Verkaik D, Cornell JE, Cunningham SE, Mohammad M, Trochta K, Lorenzo C, Folli F, Bansal S, Fanti P. Glutathione redox potential is low and glutathionylated and cysteinylated hemoglobin levels are elevated in maintenance hemodialysis patients. Transl Res. 2013 Jul;162(1):16-25. doi: 10.1016/j.trsl.2012.12.014. Epub 2013 Jan 17.

  PMID: 23333585 RESULT

• Cunningham SE, Verkaik D, Gross G, Khazim K, Hirachan P, Agarwal G, Lorenzo C, Matteucci E, Bansal S, Fanti P. Comparison of Nutrition Profile and Diet Record Between Veteran and Nonveteran End-Stage Renal Disease Patients Receiving Hemodialysis in Veterans Affairs and Community Clinics in Metropolitan South-Central Texas. Nutr Clin Pract. 2015 Oct;30(5):698-708. doi: 10.1177/0884533615575046. Epub 2015 Apr 21.

  PMID: 25899538 RESULT

• Fanti P, Giustarini D, Rossi R, Cunningham SE, Folli F, Khazim K, Cornell J, Matteucci E, Bansal S. Dietary Intake of Proteins and Calories Is Inversely Associated With The Oxidation State of Plasma Thiols in End-Stage Renal Disease Patients. J Ren Nutr. 2015 Nov;25(6):494-503. doi: 10.1053/j.jrn.2015.06.003. Epub 2015 Jul 31.

  PMID: 26235932 RESULT

• Giustarini D, Galvagni F, Orlandini M, Fanti P, Rossi R. Immediate stabilization of human blood for delayed quantification of endogenous thiols and disulfides. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:51-8. doi: 10.1016/j.jchromb.2016.02.009. Epub 2016 Feb 8.

  PMID: 26896310 RESULT

• Khazim K, Gorin Y, Cavaglieri RC, Abboud HE, Fanti P. The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo. Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F691-700. doi: 10.1152/ajprenal.00028.2013. Epub 2013 Jun 26.

  PMID: 23804455 RESULT

MeSH Terms

Conditions

Diabetic Nephropathies; Proteinuria

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; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Shweta Bansal
• Organization: VA- STVHCS

bansals3@uthscsa.edu

2105674700

Study Officials

• Paolo Fanti, MD

  South Texas Health Care System, San Antonio, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 23, 2010
• Study Start: January 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: December 1, 2016
• Last Updated: October 19, 2018
• Results First Posted: March 31, 2017

Record last verified: 2018-09

Locations

US (1)