Study of the Role of Pomegranate Juice Ellagitannins in the Modulation of Inflammation in Inflammatory Bowel Disease

Study Overview
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Brief Summary
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The aim of this research is to study the effects of a pomegranate juice on calprotectin levels in patients suffering of inflammatory bowel disease (IBD) in clinical remission. Fecal calprotectin levels, surrogate marker of mucosal inflammation, will be measured from baseline to 12 weeks later (end of intervention). Systemic and mucosal changes of biochemical and molecular inflammatory response markers will be also assessed.

Detailed Description
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The main purpose of the intervention trial is to assess the possible effect of pomegranate juice consumption on reducing fecal calprotectin (FC) levels in volunteers suffering from IBD with a high risk of clinical relapse. In detail, the objectives of this intervention are as follows: (i) assessing the changes in FC levels in the two groups (active treatment, control) from baseline to 12 weeks later (primary outcome); (ii) investigating the systemic and mucosal modifications of selected biochemical and molecular inflammatory response markers in the two groups after 12 weeks of the intervention compared with baseline (secondary outcomes); (iii) evaluating circulating and urinary ellagitannin-derived metabolites from regular pomegranate juice consumption in the two groups before and after the intervention. The detailed study protocol is published in the Trials journal.

Official Title
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New Insight and Knowledge on Anti-inflammatory Effectiveness of Dietary Phenolics (NIKE)

Conditions
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Crohn's Disease, Ulcerative Colitis

Intervention / Treatment
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* Other: 100% pomegranate juice
* Other: placebo beverage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Ulcerative Colitis (diagnosed on the base of clinic, endoscopic, and histologic criteria) in clinical remission (SCCAI = 0) from at least three months and in stable therapy (without therapeutic modifications in the three previous months) with mesalazine, immunomodulators and/or biologics. Patients affected by Crohn's Disease, particularly involving sigmoid colon and rectum (diagnosed on the base of clinic, endoscopic, and histologic criteria) in clinical remission (CDAI < 150) from at least three months and in stable therapy (without therapeutic modifications in the three previous months) with mesalazine A, immunomodulators and/or biologics. Fecal calprotectin at baseline ≥ 100 microg/g. Signed informed consent. Exclusion Criteria: Patients affected by Ulcerative Colitis and Crohn's Disease with severe endoscopic disease activity (Ulcerative Colitis: Mayo Endoscopic Score = 3; Crohn's Disease: Simple Endoscopic Score SES-CD > 15). Patients on steroid therapy in the two previous months. Patients in therapy with warfarin or other anticoagulants. Known or supposed hypersensitivity to fruit and/or juice of pomegranate. Women in fertile age which refuse to use contraceptives specified in the study (oral contraception, IUD) and breastfeed women. Diabetic patients and other patients with severe clinical conditions which the investigator consider to contraindicate patient participation at the study. Therapy modifications and/or assumption of experimental therapies within three months before the study inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomegranate juice<br>The pomegranate juice is 100% pomegranate juice, not from concentrate. | Other: 100% pomegranate juice<br>* 125 mL of 100% pomegranate juice twice daily for 12 weeks<br>|
| Placebo Comparator: Placebo beverage<br>The placebo beverage consists in water added with sugar and citric acid. | Other: placebo beverage<br>* 125 mL of placebo beverage twice daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fecal calprotectin | Change from baseline in fecal neutrophil-derived protein calprotectin, surrogate marker of mucosal improvement, after 12 weeks of consumption of experimental or placebo beverage, in subjects affected by IBD in clinical remission. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma concentration of ellagitannin metabolites | Change from baseline in plasma concentration of ellagitannin metabolites after 12 weeks of intervention. | Baseline and 12 weeks | 
| Changes in circulating cytokines levels | Change from baseline in plasma levels of cytokines after 12 weeks of intervention. | Baseline and 12 weeks | 
| Changes in circulating trimethylamine-N-oxide (TMAO) levels | Change from baseline in plasma levels of TMAO after 12 weeks of intervention. | Baseline and 12 weeks | 
| Changes in gene expression levels in peripheral blood mononuclear cells (PBMC) | Change from baseline in expression levels of selected genes in PBMC by qPCR after 12 weeks of intervention. | Baseline and 12 weeks | 
| Changes in gene expression levels in intestinal biopsies | Change from baseline in expression levels of selected genes in intestinal biopsies by qPCR after 12 weeks of intervention. | Baseline and 12 weeks | 
| Changes in urinary ellagitannin metabolite excretion | Change from baseline in urinary ellagitannin metabolite excretion after 12 weeks of intervention. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroenteritis, Fruit, Biomarkers, Colitis, Colitis, Ulcerative, Colonic Diseases, Crohn Disease, Digestive System Diseases, Fruit and Vegetable Juices, Gastrointestinal Diseases, Humans, Hydrolysable Tannins, Inflammation, Inflammatory Bowel Disease, Intestinal Diseases, Punicaceae