Vitamins C and Vitamin E and Cardiovascular Risk

This study has been completed.
Sponsor:
Collaborator:
American Diabetes Association
Information provided by:
University of New Mexico
ClinicalTrials.gov Identifier:
NCT00362518
First received: August 9, 2006
Last updated: September 2, 2008
Last verified: September 2008

August 9, 2006
September 2, 2008
July 2004
June 2007   (final data collection date for primary outcome measure)
The goal is to determine the effects of the vitamin C and vitamin E on surrogate markers of atherosclerosis following an atherogenic meal in type 2 diabetes [ Time Frame: 2 months ] [ Designated as safety issue: No ]
The goal is to determine the effects of the suppression of gamma vitamin E by alpha vitamin E on surrogate markers of atherosclerosis following an atherogenic meal in type 2 diabetes
Complete list of historical versions of study NCT00362518 on ClinicalTrials.gov Archive Site
To determine changes in surrogate markers of atherosclerosis in type 2 diabetes [ Time Frame: 2 months ] [ Designated as safety issue: No ]
To determine changes in surrogate markers of atherosclerosis in type 2 diabetes
Not Provided
Not Provided
 
Vitamins C and Vitamin E and Cardiovascular Risk
Vitamin C and Vitamin E Therapy in Type 2 Diabetes and Cardiovascular Risk

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Diabetes
  • Dietary Supplement: Study Arm A
    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.
    Other Name: Study Arm A
  • Dietary Supplement: Study Arm B
    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).
    Other Name: Study Arm B
  • Dietary Supplement: Study Arm C
    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).
    Other Name: Study Arm C
  • Dietary Supplement: Study Arm D
    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).
    Other Name: Study Arm D
  • Placebo Comparator: 1
    Study Arm A - Control: no vitamins (placebo only).
    Intervention: Dietary Supplement: Study Arm A
  • Active Comparator: 2
    Study Arm B - Low Dose: Vitamin C 250 mg, Vitamin E 200 IU
    Intervention: Dietary Supplement: Study Arm B
  • Active Comparator: 3
    Study Arm C - Medium Dose: Vitamin C 500 mg, Vitamin E 400 IU
    Intervention: Dietary Supplement: Study Arm C
  • Active Comparator: 4
    Study Arm D - High Dose: Vitamin C 1000 mg, Vitamin E 800 IU.
    Intervention: Dietary Supplement: Study Arm D
Gutierrez AD, de Serna DG, Robinson I, Schade DS. The response of gamma vitamin E to varying dosages of alpha vitamin E plus vitamin C. Metabolism. 2009 Apr;58(4):469-78.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
March 2008
June 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The study will enroll subjects, both men and women with type 2 diabetes of at least six months duration. The age of enrolled subjects will range from 21-60 years old. An HbA1c blood test must show that the person's diabetes is under control. Eligible subjects must have normal electrocardiogram tracings and normal hematological, electrolyte and liver laboratory results at screening. Females of childbearing age must agree to use an effective form of birth control throughout the study period.

Exclusion Criteria:

  • Subjects will be excluded if they have known vascular disease, uncontrolled hypertension (>140/90 mmHg), marked hyperlipidemia (serum low density lipoprotein > 4.1 mmol/L or serum triglycerides > 7.8 mmol/L), and a body mass index greater than 40 kg/m2 (range 27-40). Other important exclusion criteria are cigarette smoking, volunteers taking Coumadin, and recent use of antioxidant supplements or aspirin. Females who are pregnant or breastfeeding will be excluded. People cannot participate in this study if they are taking medications (other than antidiabetic medications) which may affect blood sugar.
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00362518
04-319, 7-04-CR-41
Yes
David S. Schade, University of New Mexico
University of New Mexico
American Diabetes Association
Principal Investigator: David S Schade, M.D. University of New Mexico School of Medicine
University of New Mexico
September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP