Vitamins C and Vitamin E and Cardiovascular Risk

NCT ID: NCT00362518

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2008-03-31

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.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Study Arm A - Control: no vitamins (placebo only).

Group Type: PLACEBO_COMPARATOR

Study Arm A

Intervention Type: DIETARY_SUPPLEMENT

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.

2

Study Arm B - Low Dose: Vitamin C 250 mg, Vitamin E 200 IU

Group Type: ACTIVE_COMPARATOR

Study Arm B

Intervention Type: DIETARY_SUPPLEMENT

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).

3

Study Arm C - Medium Dose: Vitamin C 500 mg, Vitamin E 400 IU

Group Type: ACTIVE_COMPARATOR

Study Arm C

Intervention Type: DIETARY_SUPPLEMENT

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).

4

Study Arm D - High Dose: Vitamin C 1000 mg, Vitamin E 800 IU.

Group Type: ACTIVE_COMPARATOR

Study Arm D

Intervention Type: DIETARY_SUPPLEMENT

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

University of New Mexico

OTHER

Sponsor Role: lead

Responsible Party

University of New Mexico

Principal Investigators

David S Schade, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of New Mexico School of Medicine

Locations

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

Countries

United States

References

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. doi: 10.1016/j.metabol.2008.11.003.

Reference Type: DERIVED

PMID: 19303966 (View on PubMed)

Other Identifiers

7-04-CR-41

Identifier Type: -

Identifier Source: secondary_id

04-319

Identifier Type: -

Identifier Source: org_study_id