Vitamins C and Vitamin E and Cardiovascular Risk

Study Overview
=================
Brief 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.

Official Title
-----------------
Vitamin C and Vitamin E Therapy in Type 2 Diabetes and Cardiovascular Risk

Conditions
-----------------
Diabetes

Intervention / Treatment
-----------------
* Dietary Supplement: Study Arm A
* Dietary Supplement: Study Arm B
* Dietary Supplement: Study Arm C
* Dietary Supplement: Study Arm D


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Study Arm A - Control: no vitamins (placebo only). | Dietary Supplement: Study Arm A<br>* 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.<br>|
| Active Comparator: 2<br>Study Arm B - Low Dose: Vitamin C 250 mg, Vitamin E 200 IU | Dietary Supplement: Study Arm B<br>* 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).<br>|
| Active Comparator: 3<br>Study Arm C - Medium Dose: Vitamin C 500 mg, Vitamin E 400 IU | Dietary Supplement: Study Arm C<br>* 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).<br>|
| Active Comparator: 4<br>Study Arm D - High Dose: Vitamin C 1000 mg, Vitamin E 800 IU. | Dietary Supplement: Study Arm D<br>* 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).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine changes in surrogate markers of atherosclerosis in type 2 diabetes |  | 2 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
atherosclerosis, vitamin C, vitamin E