Vitamins C and Vitamin E and Cardiovascular Risk
Condition: Diabetes
Study type: Interventional
Phase: Phase 3

Summary: 
      The proposed study will examine the hypothesis that vitamin C and vitamin E given to type 2
      diabetic individuals will provide effective anti-inflammatory, anti-thrombotic, and
      anti-oxidative atherosclerotic protection when administered at the optimal dose as determined
      by surrogate markers of inflammation, hypercoagulability, and oxidation.
    

Detailed description: 
      This American Diabetes Association research project is to determine why there are discrepant
      results between individual studies of Vitamin E and C in both animals and humans compared
      with the results obtained in large randomized human trials using Vitamin E.

      Subjects: The study will enroll subjects (both men and women) with type 2 diabetes of at
      least six months duration. An outpatient screening test will utilize the following: a
      complete history and physical examination, an EKG, a urine hcG (only for women of
      childbearing age), and the following blood tests: CBC, Chem-20, lipid profile, hemoglobin
      A1C, and C-peptide stimulation test. Subjects will be excluded if they have known vascular
      disease, uncontrolled hypertension (>140/90 mmHg) or marked hyperlipidemia (serum low density
      lipoprotein > 4.1 mmol/L or serum triglycerides > 7.8 mmol/L). Eligible patients must have
      normal electrocardiogram tracings and normal screening test results (described above). Other
      important exclusion criteria are cigarette smoking, volunteers taking Coumadin, and recent
      use of antioxidant supplements or aspirin. All patients will provide written informed consent
      before enrollment as approved by the University of New Mexico Human Research Review
      Committee.

      Surrogate Markers: Based on our preliminary data and the published medical literature, it is
      extremely likely that vitamins C and E will modify all three contributors to atherosclerosis:
      Oxidative stress, Hypercoagulability, and Inflammation. Therefore, as shown in the table
      above, we have included standard surrogate markers for all three of these contributors.

      Specific Aim: Determine the optimal oral dose of vitamin C and vitamin E relative to the
      consumption of an atherogenic high fat supper in type 2 diabetic individuals. These data are
      necessary in order to design prospective clinical trials in which vitamins are given to
      prevent or delay atherosclerotic events. One reason that published clinical trials
      demonstrate conflicting results may be the different dosages of vitamins that have been
      utilized. In the following study, we will utilize our high fat (simulated Big Mac) meal to
      assess the beneficial effects of these vitamins on surrogate markers of atherosclerosis.
      Three dosages of vitamins will be utilized in order to determine the optimal dosage.

      The three dosages to be tested are 1) low dose - vitamin C 250mg, vitamin E 200 IU 2) medium
      dose - vitamin C 500 mg, vitamin E 400 IU and 3) high dose - vitamin C 1000mg, vitamin E 800
      IU. The results will be compared to a control meal study in which only placebo (hence, no
      vitamins) is administered. The vitamins will be administered before breakfast on each study
      day.
    

Intervention name(s): Study Arm A; Study Arm B; Study Arm C; Study Arm D
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Control: no vitamins (placebo only). This study will provide baseline metabolic and surrogate marker changes that are caused by the high fat meal. Study arms B, C, and D will be statistically compared to this study.; This study arm will provide information on the response of atherogenic surrogate markers to a high fat supper when a low dosage form of vitamin C is administered (250 mg) and Vitamin E (200 IU).; This study arm will provide information on the response of atherogenic surrogate markers to a high fat supper when a medium dosage form of vitamin C administered (500 mg)and Vitamin E (400 IU).; This study arm will provide information on the response of atherogenic surrogate markers to a high fat supper when a high dosage form of vitamin C is administered (1000 mg) and Vitamin E (800 IU).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: atherosclerosis; vitamin C; vitamin E