NCT01265563

N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy

Correction of Glutathione Deficiency for Treatment of Diabetic Nephropathy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 108 (actual)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 18 Years – 76 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Oxidative stress and glutathione (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 T2DM and related nephropathy. The investigators 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 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 Nephropathy
• Proteinuria
• Oxidative Stress

Interventions

Type	Name	Description
DRUG	N-acetylcysteine placebo and silibin placebo	Dietary Supplement: N-acetylcysteine placebo excipient and silibin placebo orally twice daily for three months
DRUG	N-acetylcysteine active and silibin placebo	Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin placebo orally twice a day for three months
DRUG	N-acetylcysteine placebo and silibin active	Dietary Supplement: silibin 480 mg orally twice daily and N-acetylcysteine placebo orally twice a day for three months
DRUG	N-acetylcysteine active and silibin active	Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 480 mg orally twice daily for three months
DRUG	N-acetylcysteine active + high-dose silibin active	Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 960 mg orally twice daily for three months

Timeline

• Start date: 2011-01-01
• Primary completion: 2015-02-01
• Completion: 2016-12-01
• First posted: 2010-12-23
• Last updated: 2018-10-19
• Results posted: 2017-03-31

Locations

1 site across 1 country: United States