N-Acetylcysteine and Milk Thistle for Treatment of Diabetic Nephropathy
Condition: Diabetic Nephropathy; Proteinuria; Oxidative Stress
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Proteinuria
Intervention: N-acetylcysteine placebo and silibin placebo; N-acetylcysteine active and silibin placebo; N-acetylcysteine placebo and silibin active; N-acetylcysteine active and silibin active; N-acetylcysteine active + high-dose silibin active
Intervention description: Dietary Supplement: N-acetylcysteine placebo excipient and silibin placebo orally twice daily for three months; Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin placebo orally twice a day for three months; Dietary Supplement: silibin 480 mg orally twice daily and N-acetylcysteine placebo orally twice a day for three months; Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 480 mg orally twice daily for three months; Dietary Supplement: N-acetylcysteine 600 mg orally twice daily and silibin 960 mg orally twice daily for three months
Intervention MeSH terms: Acetylcysteine; Silybin; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Maximum age: 76 Years
Healthy volunteers: No
Keywords: silymarin; glutathione; diabetic nephropathies; oxidative stress; N-acetylcysteine; protein tholation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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)

               -  Phenytoin

               -  Warfarin

               -  Prescription-grade vitamin E, vitamin C, systemic steroids, and/or non-steroidal
                  anti-inflammatory agents

               -  Over-the-counter vitamin E, vitamin C, and/or non-steroidal anti-inflammatory
                  agents

               -  Over-the-counter antioxidants supplements including:

                    -  Lipoic acid

                    -  Coenzyme Q10

                    -  N-acetyl-cysteine (NAC)

                    -  Glutathione (GSH)

                    -  Chromium

                    -  Fish-oil extracts (omega-3 fatty acids)

                    -  Soy extracts (isoflavones)

                    -  Milk thistle extract (silymarin)

                    -  Green-tea preparations

                    -  Pomegranate extracts

                    -  Grape extracts

                    -  Prickly pear extract

          -  Active coronary artery disease or cerebral vascular disease within 3 months prior to
             signing the informed consent

          -  Hepatic dysfunction as defined by abnormal total bilirubin or liver enzymes (ALT, AST)
             >2 times upper limit of normal range

          -  Active malignancy

          -  History of drug or alcohol dependency

          -  Psychiatric or neurological condition, preventing aware consent to the study and/or
             adherence to the study protocol

          -  Unwillingness to practice birth control throughout the study

          -  Participation to another clinical study within 1 month prior to signing the informed
             consent form

          -  Planned move to outside the study area, surgery or radiographic studies utilizing
             iodine-based contrast material within the next one year