Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00021970 |
| Other study ID # |
979 |
| Secondary ID |
R01HL068397 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
August 10, 2001 |
| Last updated |
February 29, 2016 |
| Start date |
April 2001 |
| Est. completion date |
March 2005 |
Study information
| Verified date |
February 2016 |
| Source |
University of Minnesota - Clinical and Translational Science Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial Summary
To determine the effects of four treatments (placebo, a vitamin E and C regimen, a hormone
replacement regimen, and a combined vitamin/hormone replacement regimen) on specific markers
of oxidative damage in coronary arteries of postmenopausal women.
Description:
BACKGROUND:
Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial
infarctions, with efficacy related to dosage and the duration of treatment. Its effects may
be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity.
Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent
reduction in oxidative damage, a primary feature of atherosclerotic lesions.
Estrogen/hormone replacement therapy (HRT) also may reduce oxidative damage, and it may
enhance the effect of vitamin E and C. These hypotheses are supported by studies defining
oxidation-dependent accumulation of lipids in developing atherosclerosis; the detection of
oxidative damage products, such as oxidized-LDL particles, in human atherosclerotic lesions;
and clinical studies associating antioxidant or estrogen supplementation with reductions in
oxidative damage cardiovascular disease. Nevertheless, no human studies have evaluated the
effect of long-term VitE/C treatment, which has been reported as being the most effective
prevention factor by epidemiologic studies, on specific. biochemical markers of oxidative
damage and concurrently their association with recurrent cardiovascular disease. In
addition, no studies have characterized the effect of long-term HRT on markers of oxidative
damage or HRT's potential synergistic effect with VitE/C therapy.
DESIGN NARRATIVE:
The study assayed specific biochemical measures of oxidative damage (all markers at closeout
and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin
and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior
cardiovascular disease event to placebo, Vitamin E/C, hormone replacement therapy (HRT) or
the combination of VitE/C and HRT. WAVE determined the efficacy of these treatments on
quantitative angiographic evaluation of minimal coronary artery diameter performed at
baseline and at the final visit to be completed during the first 10 months of 2001. The
ancillary study measured oxidation products from several classes of compounds (lipids by
F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by
8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to
atherogenesis. In addition, inflammation with C-reactive protein, platelet activation with
p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the
study population were integrated into the assessment of oxidative damage in WAVE. By
measuring these various factors and by assessing oxidative damage in several classes of
compounds, the authors tested the relationships among specific pathways of oxidative damage,
supplemental VitE/C and/or HRT and other risk factors upon the progression of established
macrovascular disease.
