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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Serrated Adenomas; Colorectal Tubular Adenomas; Colorectal Villous Adenomas; Colorectal Tubulovillous Adenomas
• Intervention / Treatment: Dietary supplement: Green tea extract of Camellia Sinensis; Dietary supplement: Green tea extract of Camellia Sinensis followed by placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1001
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Aalen, Germany, 73430
    • Ostalb-Klinikum Aalen, Medizinische Klinik 1, Sekretariat Prof. Kleber
  • Altenburg, Germany, 04600
    • Klinikum Altenburger Land, Gastroenterologie
  • Augsburg, Germany, 86156
    • Klinikum Augsburg, III. Med. Klinik
  • Bietigheim-Bissingen, Germany, 74321
    • Krankenhaus Bietigheim-Bissingen, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie
  • Buchholz, Germany, 21244
    • Krankenhaus Buchholz, Abteilung Innere Medizin
  • Cologne, Germany
    • Kliniken der Stadt Köln gGmbH, Krankenhaus Holweide -Medizinische Klinik-
  • Esslingen, Germany, 73730
    • Klinikum Esslingen, Klinik für Innere Medizin, Onkologie, Gastroenterologie
  • Greifswald, Germany, 17475
    • Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald, Klinik und Poliklinik für Innere Medizin A
  • Halle, Germany, 06108
    • Dr. Zeisler, Praxis für Innere Medizin und Gastroenterologie
  • Halle, Germany, 06108
    • Dres. Fechner/Behrens/Steudel - Gastroenterologisch-Onkologische Praxisklinik
  • Halle, Germany, 06110
    • Dr. Frank-Gleich Praxis für Innere Medizin und Gastroenterologie
  • Halle, Germany, 06120
    • Universitätsklinikum Halle, Klinik für Innere Medizin I
  • Ludwigsburg, Germany, 71640
    • Klinikum Ludwigsburg, Medizinische Klinik I
  • Mannheim, Germany, 68163
    • Diakoniekrankenhaus Mannheim, Medizinische Klinik II
  • Munich, Germany, 81675
    • II. Medizinische Klinik und Poliklinik der TU München, Klinikum rechts der Isar
  • Mühldorf, Germany, 84453
    • Klinik Mühldorf Abt.Gastroenterologie
  • München, Germany, 81525
    • Klinikum Bogenhausen, Interdisziplinäre Onkologische Tagklinik
  • Pinneberg, Germany, 25421
    • Regio Kliniken Pinneberg
  • Straubing, Germany, 94315
    • Klinikum St. Elisabeth, I. Medizinische Klinik
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm, Klinik für Innere Medizin I
  • Wesel, Germany, 46485
    • Evangelisches Krankenhaus Wesel, Abteilung Innere Medizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Green tea extract; 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; 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
Placebo Comparator: Placebo; Placebo, packed in hard gelatine capsules, bid for 3 years	Dietary supplement: Green tea extract of Camellia Sinensis followed by placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Collaborators: University of Ulm; Deutsche Krebshilfe e.V., Bonn (Germany); KKS Netzwerk
• Investigators: Study Chair: Julia Stingl, Prof.Dr.med, Federal Institute for Drugs and Medical Devices, Bonn, Germany; Principal Investigator: Thomas Seufferlein, Prof.Dr.med., University Hospital Ulm, Ulm, Germany

Publications and helpful links

General Publications

• Stingl JC, Ettrich T, Muche R, Wiedom M, Brockmoller J, Seeringer A, Seufferlein T. Protocol for minimizing the risk of metachronous adenomas of the colorectum with green tea extract (MIRACLE): a randomised controlled trial of green tea extract versus placebo for nutriprevention of metachronous colon adenomas in the elderly population. BMC Cancer. 2011 Aug 18;11:360. doi: 10.1186/1471-2407-11-360.
• Seufferlein T, Ettrich TJ, Menzler S, Messmann H, Kleber G, Zipprich A, Frank-Gleich S, Algul H, Metter K, Odemar F, Heuer T, Hugle U, Behrens R, Berger AW, Scholl C, Schneider KL, Perkhofer L, Rohlmann F, Muche R, Stingl JC. Green Tea Extract to Prevent Colorectal Adenomas, Results of a Randomized, Placebo-Controlled Clinical Trial. Am J Gastroenterol. 2022 Jun 1;117(6):884-894. doi: 10.14309/ajg.0000000000001706. Epub 2022 Feb 25.
• Scholl C, Lepper A, Lehr T, Hanke N, Schneider KL, Brockmoller J, Seufferlein T, Stingl JC. Population nutrikinetics of green tea extract. PLoS One. 2018 Feb 21;13(2):e0193074. doi: 10.1371/journal.pone.0193074. eCollection 2018.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: May 23, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Epigallocatechin gallate; polyphenol; Green tea; EGCG; colon cancer prevention; catechin; colorectal adenoma; adenoma prevention
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Adenoma, Villous
• Other Study ID Numbers: MIRACLE