Efficacy of Vitamin D in Colorectal Cancer Chemoprevention

Vitamin D’s ability to prevent colorectal cancer (CRC) has been suspected for nearly 30 years, but has never been directly studied in humans. The biologically active version of vitamin D, 1,25(OH)2D3, cannot be readily used in humans because of its tendency to cause serum calcium levels to rise. In contrast, 25(OH)D3 (ie calcifediol) does not have this side effect. The investigators previous research suggests that the enzyme necessary to convert 25(OH)D3 (calcifediol) into active 1,25(OH)D3 is present in cells lining the large intestine (colon).
Aberrant crypt foci (ACF) are very small (ie microscopic) collections of abnormally shaped cells that are a commonly used marker of CRC risk. Screening colonoscopy at UIC routinely uses methods that allow ACF counting to be done as a part of standard practice. ACF’s are not fixed, like polyps or cancers, but can disappear as a person’s risk for developing CRC decreases.
The investigators propose giving patient’s with 10 or more ACF’s 25(OH)D3 (calcifediol) or placebo, and determining if there is a drug-dependant decrease in ACF number. The primary objective is to determine whether 25(OH)D3 (calcifediol) supplementation, compared to placebo, causes significant reduction of ACF number from baseline levels. The primary endpoint will be change in ACF number.

维生素D预防结直肠癌（colorectal cancer, CRC）的潜在作用已被推测近30年，但始终未在人体中开展直接研究。具有生物活性的维生素D形式1,25(OH)2D3，因易导致血清钙水平升高，难以在人体中安全应用。与之相对，25(OH)D3（即骨化二醇，calcifediol）并无此类副作用。研究团队此前的研究显示，将25(OH)D3（骨化二醇）转化为活性形式1,25(OH)2D3所需的酶，可在大肠（结肠）内壁细胞中检出。
异常隐窝病灶（Aberrant crypt foci, ACF）是一类体积微小（仅可在显微镜下观测到）的形态异常细胞集落，是临床常用的结直肠癌风险标志物。伊利诺伊大学芝加哥分校（University of Illinois Chicago, UIC）的常规筛查结肠镜检查中，已将ACF计数纳入标准操作流程。异常隐窝病灶并非如息肉或癌症般固定不变，而是会随着个体结直肠癌发病风险降低而消失。
本研究团队拟为ACF数量≥10个的患者给予25(OH)D3（骨化二醇）或安慰剂，并评估ACF数量是否随药物干预出现显著下降。本研究的主要目标为明确：相较于安慰剂，补充25(OH)D3（骨化二醇）是否可使ACF数量较基线水平出现显著减少。本研究的主要终点为ACF数量的变化值。