The MIRACLE trial: A randomized, controlled trial comparing green tea extract versus placebo for the prevention of metachronous colon adenomas in a screening population.

TPS786 Background: Prevention of colorectal cancer is a major health care issue. After polypectomy there is an increased risk of polyp recurrence and various means of chemoprevention have been tried to prevent this. NSAIDs have been shown to be effective but confer side effects such as gastrointestinal bleeding. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and some clinical trials. However, their value in preventing colorectal polyps has not been demonstrated in a large, randomized trial. The beneficial safety profile of decaffeinated green tea extract and accumulating evidence of its cancer preventive potential justify and require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as nutritional supplement in colon cancer prevention. Methods: Randomized, double blinded, placebo-controlled, multicenter trial. After a one month run-in period with verum, 918 patients (age: 50-80 years) who have undergone polypectomy within the last 6 months will be randomized to receive either decaffeinated green tea extract (containing 150 mg epigallocatechin gallate (EGCG) two times daily) or placebo over a period of three years. Primary outcome: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous, serrated lesions) at the 3 year follow-up colonoscopy. Secondary outcomes: Occurrences, number, localization, size and histological subtypes of adenomas, frequency of colorectal carcinoma. In addition, genetic and biochemical biomarkers in blood samples and genetic alterations (Ras, B-raf, microRNAs) in tissue samples of adenomas will be analyzed (biobanking subprojects). Additionally, nutrikinetics and nutrigenetics of EGCG and other catechins will be assessed in healthy volunteers. Patient recruitment has started in November 2011. At September 2014, 785 patients were recruited and 651 patients were randomized. We expect the last patient out in Spring 2018. (Trial identifier NCT01360320) Clinical trial information: NCT01360320.