Clinical Trial: Use of Mucomyst to Ameliorate Oxidant Stress in Diabetics With Proteinuria
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Use of Mucomyst (NAC) to Ameliorate Oxidant Stress in Diabetic Patients as Measurable by Surrogate Serum Markers
Brief Summary: The study will look at the effect of 30 days of treatment of 15 diabetics with proteinuria with N-acetylcysteine ( Mucomyst ) at a dose of 1 gm twice a day by mouth. The primary outcome that will be measured is change in the oxidant stress as measurable by changes in the serum level of isoprostane, Glutathione peroxidase, aconitase and Total oxidant stress. Secondary outcomes measured will be changes in proteinuria and kidney function as measured by spot urine pr/cr and estimated GFR by MDRD formula.
Detailed Summary:
Mucomyst (Acetylcysteine) for amelioration of diabetic nephropathy
Hypothesis:
Treatment with Mucomyst over several months will reduce the oxidant stress and thereby reduce the proteinuria and the progression of renal failure in patients with diabetic nephropathy.
Rationale:
Mucomyst or Acetylcysteine has now been found to be beneficial in ameliorating radio-contrast induced acute renal failure in several different studies (ref 1) The beneficial effects of Mucomyst is most likely due to its antioxidative properties. Oxidative stress plays a major role in diabetic complication especially in diabetic nephropathy.
In a recent in vitro study Acetylcysteine ameliorated the deleterious effects of albumin on cultured renal proximal tubular epithelial cells. Murine proximal tubular cells were treated with albumin (30 mg/ml medium) for various lengths of time. The results showed that albumin could activate Stat1 and Stat5 within 15 min in proximal tubular cells. The activation of STATs was mediated mostly by Jak2 and required no protein synthesis. In addition, activation of Stat1 occurred even after neutralization of IFN- . The activation of STATs was inhibited by N-acetyl-L-cysteine, a precursor of glutathione and a reactive oxygen species (ROS) scavenger, and fluorescence-activated cell sorter analysis showed upregulation of intracellular ROS after albumin overloading, suggesting that albumin per se could generate ROS in proximal tubular cells. The activation of STATs occurred by way of the ROS generating system, and especially through the membrane-bound NADPH oxidase system. Reduced activities of glutathione peroxidase and catalase could also be responsible for the accumulation of
Sponsor: VA Office of Research and Development
Current Primary Outcome: This research will test the possibility the Mucomyst given by mouth for a month will decrease oxidative stress and slow the disease.
Original Primary Outcome: This research will test the possibility the Mucoyst given by mouth for a month will decrease oxidative stress and slow the disease.
Current Secondary Outcome: Reduction of proteinuria
Original Secondary Outcome: Same as current
Information By: VA Office of Research and Development
Dates:
Date Received: June 27, 2007
Date Started: September 2006
Date Completion:
Last Updated: May 16, 2008
Last Verified: May 2008
