Anthocyanin Extract and Phospholipid Curcumin in Colorectal Adenoma (MIRACOL)

Randomized Window of Opportunity Trial of Anthocyanin Extract and Phospholipid Curcumin in Subjects With Colorectal Adenoma

It has been shown that curcumin and cyanidin-3-glucoside (C3G) have anticancer effects. In this clinical trial we compare the affect of their combination vs placebo in a four weeks intervention before endoscopic polypectomy.

Study Overview

• Status: Completed
• Conditions: Colorectal Adenoma; Risk Reduction
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Mirtoselect® + Meriva®

Detailed Description

Colonic adenomatous polyps are pre cancer lesions and are used as intermediate markers for testing agents with potential cancer prevention.

Meriva© is a bioavailable form of curcumin, a polyphenolic compound obtained from turmeric (Curcuma longa L.) endowed with anti-inflammatory, antioxidant and antitumor effects. In vivo data indicate that curcumin formulated with phosphatidylcholine furnishes higher blood levels of parent agent than natural curcumin.

Mirtoselect©, an anthocyanin mixture from bilberry containing isolated cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, prevents intestinal adenoma formation in the Apc(Min) mouse model.

The investigators hypothesize that the combination of both agents will decrease the expression of proteins involved in colon tumorigenesis relative to placebo.

The change of biomarker expression between pre-treatment biopsy and post-treatment endoscopic resection in the target adenoma and the normal rectal mucosa will be the response measures.

The primary response measure is the change of immunohistochemical (IHC) expression of β-catenin in adenomatous tissue and normal rectal mucosa. Secondary response measures are the changes of IHC Nuclear Factor-Kβ (NFKβ), cell proliferation by Ki-67 Labeling Index and apoptosis by P53 in adenomatous and adjacent normal mucosa.

The study design is a phase II, randomized, double blind, placebo controlled, window of opportunity trial of the combination of Mirtoselect 1 gr/day+Meriva 1 gr/day or placebo. Subjects with histological confirmation of colorectal adenomatous polyps >1 cm not suitable to immediate complete removal will be enrolled in a 4-week intervention trial before endoscopic polypectomy.

The demonstration of a biological activity of the two agent combination may provide the rationale for a phase III trial aimed at reducing the risk of colon cancer in high risk subjects.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Chiavari, Italy
    • "Gastroenterologia d'urgenza ed Endoscopia digestiva" Ospedale di Lavagna ASL 4 Chiavarese
  • Genoa, Italy
    • S.S. Gastroenterologia Ospedale Villa Scassi, ASL3 Genovese
  • Genova, Italy, 16128
    • Medical Oncology Ente Ospedaliero Ospedali Galliera
  • Milan, Italy
    • Divisione di Prevenzione e Genetica Oncologica, IEO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Subjects with colorectal adenomatous polyps greater than 1 cm in maximum diameter not suitable to immediate complete removal;
• Normal renal and hepatic function;
• WHO Performance status=0;

Exclusion Criteria:

• Presence of hyperplastic polyps and/or flat adenomas;
• Subjects with pre-existing colorectal cancer;
• Presence of carcinomatous tissue in adenoma;

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: Anthocyanins+Phospholipidic Curcumin; Mirtoselect ® 500 mg tablet, 1000 mg (two oral tablets) per day and Meriva ®, 500 mg tablet, 1000 mg (two oral tablets) per day for 28 days	Dietary supplement: Mirtoselect® + Meriva®
Placebo Comparator: placeboA + placeboB; placeboA + placeboB per day for four weeks	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Beta Catenin Expression	Change of immunohistochemical expression of beta-catenin in normal and adenomatous colonic tissue	baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Biomarkes Expression	Change in immunohistochemical expression of Nuclear Factor-Kβ (NFKβ), Ki-67 Labeling Index, and P53 in normal tissue and displasia	baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Ente Ospedaliero Ospedali Galliera
• Collaborators: Fondazione Umberto Veronesi; Indena S.p.A
• Investigators: Principal Investigator: Andrea DeCensi, MD, Medical Oncology Ente Ospedaliero Ospedali Galliera

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: January 18, 2013
• First Submitted That Met QC Criteria: September 19, 2013
• First Posted (Estimated): September 23, 2013

Study Record Updates

• Last Update Posted (Actual): November 21, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenoma
• Other Study ID Numbers: GAL 02