NCT00915200

N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy

N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 114 (actual)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The study is designed to test if the combination of two potent antioxidant nutritional supplements, N-acetylcysteine and the milk thistle extract silibin, is capable of correcting the shedding of urine protein, the oxidative stress, and the inflammation in patients with type 2 diabetes mellitus and diabetic kidney disease.

Detailed description

Oxidative stress and GSH imbalance are major contributors to the pathogenesis of diabetic nephropathy. Current options for the treatment of oxidative stress in diabetic nephropathy are limited and only partially effective, thus interest in the development of new strategies is high. The study intends to test the hypothesis that combined oral supplementation of the antioxidants N-acetylcysteine (NAC) and milk thistle flavonolignan silibin (as silibin-phosphatidylcholine) will reduce proteinuria and urinary and systemic manifestations of oxidative stress and inflammation, which are characteristically observed in patients with type 2 diabetes mellitus and related nephropathy. We expect these effects to be achieved with minimal or no side effects, and with good patient tolerance. The trial is designed as a two-center, double-blind, placebo-controlled, randomized, modified-factorial dose-ranging design, five-arm pilot study in patients with Type 2 diabetes mellitus and advanced diabetic nephropathy with proteinuria. Intervention consists of three-month oral administration of NAC, silibin, and/or respective placebos for three months. Subjects are randomized to the following five intervention arms: (A) placebo; (B) NAC; (C) silibin; (D) NAC + silibin; and (E) NAC + double-dose silibin. The primary outcome measure is urinary excretion of albumin, a marker of glomerular injury. Secondary outcome measures are alpha-1 microglobulin, a marker of tubular injury, and urinary excretion of inflammatory cytokines and C-C chemokines, i.e. markers of renal inflammation. In addition, peripheral blood monocytes from the same patients are analyzed for glutathione (GSH) content and activity of GSH metabolizing enzymes. All outcome measures are monitored in relation to both treatment allocation and prevalent blood and urine levels of the active treatment. Safety and tolerability of this combination treatment are monitored throughout the trial.

Conditions

• Diabetic Nephropathies
• Proteinuria
• Oxidative Stress

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	N-acetylcysteine	600 mg orally twice daily for three months
DIETARY_SUPPLEMENT	silibin	480 mg orally twice daily for three months
DIETARY_SUPPLEMENT	high-dose silibin	960 mg orally twice daily for three months
DIETARY_SUPPLEMENT	N-acetylcysteine placebo	excipient orally twice daily for three months
DIETARY_SUPPLEMENT	silibin placebo	excipient orally twice daily for three months

Timeline

• Start date: 2009-10-01
• Primary completion: 2016-04-01
• Completion: 2016-04-01
• First posted: 2009-06-05
• Last updated: 2016-06-27

Locations

1 site across 1 country: United States