Pomegranate Extract Supplementation in Colorectal Cancer Patients

NCT01916239 | Completed Phase 1

• 1 other identifier: CEBAS-CSIC-2
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

Pomegranate; Urolithins; Colorectal cancer; Colon cancer; Metabolite; Gene expression; microRNA; Nutraceutical; Food supplement; Polyphenol; Gut microbiota

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• IGF-1 (insulin-like growth factor-1)

  Change from baseline at 15 days

• CEA (carcnoembryonic antigen)

  Change from baseline at 15 days

• Number of patients with adverse events as a measure of safety and tolerability

  Change from baseline at 15 days

• microRNA expression profiling in colon tissues

  Change from baseline at 15 days

Study Arms (3)

Standard pomegranate extract formulation

EXPERIMENTAL

Standard pomegranate extract formulation containing 20% punicalagin

Dietary Supplement: Standard pomegranate extract formulation

Pomegranate extract formulation-1

EXPERIMENTAL

New pomegranate extract formulation-1

Dietary Supplement: Pomegranate extract formulation-1

Pomegranate extract formulation-2

EXPERIMENTAL

New pomegranate extract formulation-2

Dietary Supplement: Pomegranate extract formulation-2

Interventions

Standard pomegranate extract formulation DIETARY_SUPPLEMENT

Standard pomegranate extract formulation containing 20% punicalagin

Standard pomegranate extract formulation

Pomegranate extract formulation-1 DIETARY_SUPPLEMENT

New pomegranate extract formulation-1

Pomegranate extract formulation-1

Pomegranate extract formulation-2 DIETARY_SUPPLEMENT

New pomegranate extract formulation-2

Pomegranate extract formulation-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Research Council, Spain: lead
• Hospital Universitario Reina Sofia de Cordoba: collaborator

Study Sites (1)

Hospital General Universitario Reina Sofía

Murcia, Murcia, 30003, Spain

Location

Related Publications (2)

• 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.

  PMID: 28347564 DERIVED

• 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.

  PMID: 28183047 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Dr. Juan Carlos Espín, PhD

  National Research Council (CEBAS-CSIC, Murcia, Spain)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Research Professor

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 5, 2013
• Study Start: June 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 14, 2015

Record last verified: 2015-04

Locations

ES (1)