Pomegranate Extract Supplementation in Colorectal Cancer Patients (POMEcolon)

Phase I-II Study of Pomegranate Extract Formulations in Colorectal Cancer Patients: Metabolic and Gene Expression Profiling in Tumoral and Normal Colon Tissues

The most relevant pomegranate phenolics (ellagitannins and ellagic acid) are extensively metabolized by the human gut microbiota to yield a number of metabolites called urolithins (mainly Uro-A). Urolithins have been reported to regulate in vivo the expression of genes involved in inflammation and cancer. Our hypothesis is that urolithins can be detected in the human colon mucosa where these metabolites can exert anti-inflammatory and anti-cancer activities. After colonoscopy and diagnosis, colorectal cancer patients will consume capsules containing three different pomegranate extract formulations until surgery. The aims of this trial are:

• To evaluate the disposition of pomegranate phenolics and urolithins in tumoral and normal colon tissues.
• To evaluate gene expression profiling and protein markers in tumoral and normal colon tissues from these patients.
• To compare different pomegranate extract formulations on the above.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: Standard pomegranate extract formulation; Dietary supplement: Pomegranate extract formulation-1; Dietary supplement: Pomegranate extract formulation-2

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30003
    • Hospital General Universitario Reina Sofía

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Colorectal cancer diagnosis.
• Surgery required.
• WHO status: between 0 and 2.
• Hemoglobin >10 g/dL
• ALT >2.5-fold above the normal value.
• Serum Bilirubin >1.5-fold above the normal value.
• Creatinine <140 micromol/L

Exclusion Criteria:

• Patients who do not satisfy inclusion criteria and,
• Active pectic ulcer.
• Pregnancy or breastfeeding.
• Alcoholism.
• Chemotherapy or radiotherapy a month prior to recruitment.
• Treatment with steroids or other anti-inflammatory drugs a week prior to recruitment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard pomegranate extract formulation; Standard pomegranate extract formulation containing 20% punicalagin	Dietary supplement: Standard pomegranate extract formulation; Standard pomegranate extract formulation containing 20% punicalagin
Experimental: Pomegranate extract formulation-1; New pomegranate extract formulation-1	Dietary supplement: Pomegranate extract formulation-1; New pomegranate extract formulation-1
Experimental: Pomegranate extract formulation-2; New pomegranate extract formulation-2	Dietary supplement: Pomegranate extract formulation-2; New pomegranate extract formulation-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenolics and derived metabolites in colon tissues, plasma and urine.	Occurrence of phenolics and gut-microbiota derived metabolites in tumoral and colon tissues, urine and plasma.	Change from baseline at 15 days
Gene expression profiling in colon tissues	Gene expression profile changes in tumoral and normal colon tissues	Change from baseline at 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1 (insulin-like growth factor-1)	Change in circulating IGF-1 levels	Change from baseline at 15 days
CEA (carcnoembryonic antigen)	Change in circulating CEA levels	Change from baseline at 15 days
Number of patients with adverse events as a measure of safety and tolerability	Change in markers involved in hepatic and renal functions: GGT, AST, ALP, ALT, CPK, urate, creatinin, albumin, bilirubin, LDH.; Change in hematological variables: leucocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, mean corpuscular volume, mean platelet volume, platelets, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration.; Intolerance, dyspepsia, allergic reactions, constipation, diarrhea, abdominal pain, nausea.	Change from baseline at 15 days
microRNA expression profiling in colon tissues	microRNA (miR) expression profile change in tumoral and normal colon tissues	Change from baseline at 15 days

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Hospital Universitario Reina Sofia de Cordoba
• Investigators: Principal Investigator: Dr. Juan Carlos Espín, PhD, National Research Council (CEBAS-CSIC, Murcia, Spain)

Publications and helpful links

General Publications

• Selma MV, Gonzalez-Sarrias A, Salas-Salvado J, Andres-Lacueva C, Alasalvar C, Orem A, Tomas-Barberan FA, Espin JC. The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome. Clin Nutr. 2018 Jun;37(3):897-905. doi: 10.1016/j.clnu.2017.03.012. Epub 2017 Mar 16.
• Nunez-Sanchez MA, Gonzalez-Sarrias A, Garcia-Villalba R, Monedero-Saiz T, Garcia-Talavera NV, Gomez-Sanchez MB, Sanchez-Alvarez C, Garcia-Albert AM, Rodriguez-Gil FJ, Ruiz-Marin M, Pastor-Quirante FA, Martinez-Diaz F, Tomas-Barberan FA, Espin JC, Garcia-Conesa MT. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem. 2017 Apr;42:126-133. doi: 10.1016/j.jnutbio.2017.01.014. Epub 2017 Jan 27.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: July 30, 2013
• First Submitted That Met QC Criteria: August 1, 2013
• First Posted (Estimate): August 5, 2013

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: April 13, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Colorectal cancer; microRNA; Gut microbiota; Polyphenol; Pomegranate; Urolithins; Colon cancer; Metabolite; Gene expression; Nutraceutical; Food supplement
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CEBAS-CSIC-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No