Anthocyanin Extract and Phospholipid Curcumin in Colorectal Adenoma

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Adenoma, Risk Reduction

Intervention / Treatment
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* Dietary Supplement: Mirtoselect® + Meriva®
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Anthocyanins+Phospholipidic Curcumin<br>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®<br> <br> |
| Placebo Comparator: placeboA + placeboB<br>placeboA + placeboB per day for four weeks | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 of IHC Nuclear Factor-Kβ (NFKβ), Ki-67 Labeling Index and P53 in normal and adenomatous mucosa. |  | baseline and 4 weeks |