Clinical trial NCT01916239: Pomegranate Extract Supplementation in Colorectal Cancer Patients
Official title: Phase I-II Study of Pomegranate Extract Formulations in Colorectal Cancer Patients: Metabolic and Gene Expression Profiling in Tumoral and Normal Colon Tissues
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: Pomegranate
Urolithins
Colorectal cancer
Colon cancer
Metabolite
Gene expression
microRNA
Nutraceutical
Food supplement
Polyphenol
Gut microbiota
Lead sponsor: National Research Council, Spain
Sponsor class: OTHER_GOV
Collaborators: name: Hospital Universitario Reina Sofia de Cordoba
First posted: 2013-08-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phenolics and derived metabolites in colon tissues, plasma and urine.
timeFrame: Change from baseline at 15 days
measure: Gene expression profiling in colon tissues
timeFrame: Change from baseline at 15 days
Secondary outcomes:
measure: IGF-1 (insulin-like growth factor-1)
timeFrame: Change from baseline at 15 days
measure: CEA (carcnoembryonic antigen)
timeFrame: Change from baseline at 15 days
measure: Number of patients with adverse events as a measure of safety and tolerability
timeFrame: Change from baseline at 15 days
measure: microRNA expression profiling in colon tissues
timeFrame: Change from baseline at 15 days
Other outcomes:
Locations:
city: Murcia
country: Spain
facility: Hospital General Universitario Reina Sofía
Study officials:
affiliation: National Research Council (CEBAS-CSIC, Murcia, Spain)
name: Dr. Juan Carlos Espín, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.