Clinical trial NCT01360320: Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-
Official title: Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract -MIRACLE-
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Serrated Adenomas
Colorectal Tubular Adenomas
Colorectal Villous Adenomas
Colorectal Tubulovillous Adenomas
Keywords: Green tea
polyphenol
catechin
EGCG
Epigallocatechin gallate
colorectal adenoma
adenoma prevention
colon cancer prevention
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
Collaborators: name: University of Ulm
name: KKS Netzwerk
name: Deutsche Krebshilfe e.V., Bonn (Germany)
First posted: 2011-05-25
Enrollment: 1001
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous and serrated lesions) at the 3 year follow-up colonoscopy
timeFrame: 3 years
Secondary outcomes:
measure: Occurrences of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Number of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Size of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Localization of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Histological subtypes of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Invasive growth of colorectal adenomas or mucosal lesions
timeFrame: 3 years
measure: Incidence of colorectal carcinoma
timeFrame: 3 years
measure: Translational research
timeFrame: 3 years
measure: Toxicity and feasibility
timeFrame: 3 years
Other outcomes:
Locations:
city: Aalen
country: Germany
facility: Ostalb-Klinikum Aalen, Medizinische Klinik 1, Sekretariat Prof. Kleber
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land, Gastroenterologie
city: Augsburg
country: Germany
facility: Klinikum Augsburg, III. Med. Klinik
city: Bietigheim-Bissingen
country: Germany
facility: Krankenhaus Bietigheim-Bissingen, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie
city: Buchholz
country: Germany
facility: Krankenhaus Buchholz, Abteilung Innere Medizin
city: Cologne
country: Germany
facility: Kliniken der Stadt Köln gGmbH, Krankenhaus Holweide -Medizinische Klinik-
city: Esslingen
country: Germany
facility: Klinikum Esslingen, Klinik für Innere Medizin, Onkologie, Gastroenterologie
city: Greifswald
country: Germany
facility: Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald, Klinik und Poliklinik für Innere Medizin A
city: Halle
country: Germany
facility: Dr. Zeisler, Praxis für Innere Medizin und Gastroenterologie
city: Halle
country: Germany
facility: Dres. Fechner/Behrens/Steudel - Gastroenterologisch-Onkologische Praxisklinik
city: Halle
country: Germany
facility: Dr. Frank-Gleich Praxis für Innere Medizin und Gastroenterologie
city: Halle
country: Germany
facility: Universitätsklinikum Halle, Klinik für Innere Medizin I
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg, Medizinische Klinik I
city: Mannheim
country: Germany
facility: Diakoniekrankenhaus Mannheim, Medizinische Klinik II
city: Munich
country: Germany
facility: II. Medizinische Klinik und Poliklinik der TU München, Klinikum rechts der Isar
city: Mühldorf
country: Germany
facility: Klinik Mühldorf Abt.Gastroenterologie
city: München
country: Germany
facility: Klinikum Bogenhausen, Interdisziplinäre Onkologische Tagklinik
city: Pinneberg
country: Germany
facility: Regio Kliniken Pinneberg
city: Straubing
country: Germany
facility: Klinikum St. Elisabeth, I. Medizinische Klinik
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Klinik für Innere Medizin I
city: Wesel
country: Germany
facility: Evangelisches Krankenhaus Wesel, Abteilung Innere Medizin
Study officials:
affiliation: Federal Institute for Drugs and Medical Devices, Bonn, Germany
name: Julia Stingl, Prof.Dr.med
role: STUDY_CHAIR
affiliation: University Hospital Ulm, Ulm, Germany
name: Thomas Seufferlein, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.