N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
Condition: Diabetic Nephropathies; Proteinuria; Oxidative Stress
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Proteinuria
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): N-acetylcysteine; silibin; high-dose silibin; N-acetylcysteine placebo; silibin placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 600 mg orally twice daily for three months; 480 mg orally twice daily for three months; 960 mg orally twice daily for three months; excipient orally twice daily for three months; excipient orally twice daily for three months
Other intervention name(s): NAC; silibin-phosphatidylcholine, Siliphos; silibin-phosphatidylcholine, Siliphos; NAC placebo; silibin-phosphatidylcholine placebo, Siliphos placebo
Intervention MeSH terms: Acetylcysteine; Silybin; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diabetic Nephropathies; Proteinuria; Renal Insufficiency, Chronic; Monocytes; Oxidative stress; Inflammation; Antioxidants; Glutathione; Silymarin; Acetylcysteine; Dietary Supplements; Complementary Therapies