Pomegranate Extract Supplementation in Colorectal Cancer Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: Standard pomegranate extract formulation
* Dietary Supplement: Pomegranate extract formulation-1
* Dietary Supplement: Pomegranate extract formulation-2


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard pomegranate extract formulation<br>Standard pomegranate extract formulation containing 20% punicalagin | Dietary Supplement: Standard pomegranate extract formulation<br>* Standard pomegranate extract formulation containing 20% punicalagin<br>|
| Experimental: Pomegranate extract formulation-1<br>New pomegranate extract formulation-1 | Dietary Supplement: Pomegranate extract formulation-1<br>* New pomegranate extract formulation-1<br>|
| Experimental: Pomegranate extract formulation-2<br>New pomegranate extract formulation-2 | Dietary Supplement: Pomegranate extract formulation-2<br>* New pomegranate extract formulation-2<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pomegranate, Urolithins, Colorectal cancer, Colon cancer, Metabolite, Gene expression, microRNA, Nutraceutical, Food supplement, Polyphenol, Gut microbiota