PHASE I PREVENTION TRIAL OF ACTIVIN TM GRAPE SEED EXTRACT AS AN AROMATASE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。芳香化酶抑制剂治疗对侧乳腺癌（BC）的减少表明它们可能对BC预防有效。营养保健品是那些喜欢膳食补充剂而不是标准药物的女性的流行选择。我们的小组证明了葡萄籽提取物（GSE）的一种以前未知的抗芳香化酶作用。我们建议将其转化为人类BC化学预防试验。目的：1.确定GSE是否显著抑制绝经后妇女BC风险增加的循环雌激素，2。收集初步剂量信息，3.以确定生物利用度，以及4.以评估人体安全性和耐受性。 方法：24名受试者将在2周安慰剂对照期后接受4个剂量水平的GSE治疗12周。将在预定的时间间隔抽取血液用于血清雌激素、原花青素浓度和芳香酶抑制测定。将在GSE前后检查骨代谢和肾上腺抑制标志物，并随访症状日志。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Decreased contralateral breast cancer (BC) seen with aromatase inhibitor therapy suggests they may be effective for BC prevention. Nutriceuticals are popular alternatives for women who prefer dietary supplements over standard pharmaceuticals. Our group demonstrated a previously unknown anti-aromatase effect with grape-seed extract (GSE). We propose translation to a human BC chemoprevention trial. Objectives: 1. to determine whether GSE significantly suppresses circulating estrogens in postmenopausal women at increased BC risk, 2. to gather preliminary dose information, 3. to determine bioavailability, and 4. to evaluate safety and tolerability in humans. Methods: Twenty-four subjects will be treated with GSE at four dose levels for a 12-week period, following a 2-week placebo control period. Blood will be drawn at scheduled intervals for serum estrogen, procyanidin concentration, and aromatase inhibition assays. Markers of bone metabolism and adrenal suppression will be checked pre and post GSE, and symptom logs will be followed.