Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-

Study Overview
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Brief Summary
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This is a randomized, placebo controlled, multicentric trial to investigate the effect of diet supplementation with green tea extract containing 300mg epigallocatechin gallate (EGCG), the major polyphenol of green tea, on the recurrence of colon adenomas.

Detailed Description
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Prevention of colorectal cancer is a major health care issue because of the high incidence of this cancer. So far, pharmaceutical chemoprevention has not gained widespread acceptance due to side effects of the chemopreventive agents used. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and clinical trials. However, controlled trials demonstrating the efficacy of nutraceuticals fo the prevention of colorectal cancer are largely missing. The investigators present this randomized, placebo controlled, multicentric trial to investigate the effect of diet supplementation with green tea extract containing 300mg epigallocatechin gallate (EGCG), the major polyphenol of green tea, on the recurrence of colon adenomas. Patients who underwent polypectomy for colonic polyps will be randomized after a one month verum run-in period to receive either 150mg EGCG two times daily or placebo over the course of three years. The beneficial safety profile of decaffeinated green tea extract, the quantifiable and known active content EGCG, and the accumulating evidence on its cancer preventive potential require in our view a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this nutraceutical a top candidate for a wider use as food supplement in colon cancer prevention.

Official Title
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Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-

Conditions
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Colorectal Serrated Adenomas, Colorectal Tubular Adenomas, Colorectal Villous Adenomas, Colorectal Tubulovillous Adenomas

Intervention / Treatment
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* Dietary Supplement: Green tea extract of Camellia Sinensis
* Dietary Supplement: Green tea extract of Camellia Sinensis followed by placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 50-80 years of age Histologically confirmed colorectal adenomas or serrated lesions removed during colonoscopy within the last 6 months Good performance status (ECOG < 2) at study entrance Written informed consent. Exclusion Criteria: History of hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP) History of colon or rectal cancer, other concomitant cancers with the exemption of basalioma or curative treated cancers without actual anticancer medication. Intestinal malabsorption, short bowel syndrome or surgical bowel interventions leading to malabsorption Liver failure (hepatitis, cirrhosis, elevation of liver enzymes ALT, AST or bilirubin to more than 2.5 fold of the reference levels) Inflammatory bowel disease Regular intake of NSAIDs (also Cox2 inhibitors) for more than 3 months per year except of low-dose aspirin (100 mg per day) Immunosuppressive medication Impaired capacity to consent or who are impaired in swallowing a pill Regular consumption of green tea extract as nutritional supplement (with a content of EGCG of more than 100mg per day) of longer than 6 months during the past two years Allergic reactions towards green tea

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Green tea extract<br>Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG, bid for 3 years | Dietary Supplement: Green tea extract of Camellia Sinensis<br>* Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG Run-in period with 150mg EGCG two times daily (p.o) for 4 weeks 150mg EGCG two times daily (p.o.) over the course of three years. Colonoscopy after 3 years<br>|
| Placebo Comparator: Placebo<br>Placebo, packed in hard gelatine capsules, bid for 3 years | Dietary Supplement: Green tea extract of Camellia Sinensis followed by placebo<br>* Powdered decaffeinated green tea extract of Camellia Sinensis, packed in hard gelatine capsules containing either 150 mg EGCG Run-in period with 150mg EGCG two times daily (p.o.) for 4 weeks Placebo two times daily (p.o.) over the course of three years Colonoscopy after 3 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous and serrated lesions) at the 3 year follow-up colonoscopy |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrences of colorectal adenomas or mucosal lesions |  | 3 years | 
| Number of colorectal adenomas or mucosal lesions |  | 3 years | 
| Size of colorectal adenomas or mucosal lesions |  | 3 years | 
| Localization of colorectal adenomas or mucosal lesions |  | 3 years | 
| Histological subtypes of colorectal adenomas or mucosal lesions |  | 3 years | 
| Invasive growth of colorectal adenomas or mucosal lesions |  | 3 years | 
| Incidence of colorectal carcinoma |  | 3 years | 
| Translational research | Genetic and biochemical biomarkers for recurrence of adenoma or development of dysplasia and carcinoma (blood samples and histological in tissue samples of the colorectal lesions) | 3 years | 
| Toxicity and feasibility |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Green tea, polyphenol, catechin, EGCG, Epigallocatechin gallate, colorectal adenoma, adenoma prevention, colon cancer prevention