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Study of the Role of Pomegranate Juice Ellagitannins in the Modulation of Inflammation in Inflammatory Bowel Disease (POME2016)

Primary Purpose

Crohn's Disease, Ulcerative Colitis

Status

Active

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

100% pomegranate juice

placebo beverage

About this trial

This is an interventional basic science trial for Crohn's Disease focused on measuring Biomarkers, Colitis, Colitis, Ulcerative, Colonic Diseases, Crohn Disease, Digestive System Diseases, Fruit, Fruit and Vegetable Juices, Gastroenteritis, Gastrointestinal Diseases, Humans, Hydrolysable Tannins, Inflammation, Inflammatory Bowel Disease, Intestinal Diseases, Punicaceae

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

U.O. Gastroenterologia - Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pomegranate juice

Placebo beverage

Arm Description

The pomegranate juice is 100% pomegranate juice, not from concentrate.

The placebo beverage consists in water added with sugar and citric acid.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Changes in plasma concentration of ellagitannin metabolites

Change from baseline in plasma concentration of ellagitannin metabolites after 12 weeks of intervention.

Changes in circulating cytokines levels

Change from baseline in plasma levels of cytokines after 12 weeks of intervention.

Changes in circulating trimethylamine-N-oxide (TMAO) levels

Change from baseline in plasma levels of TMAO after 12 weeks of intervention.

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.

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.

Changes in urinary ellagitannin metabolite excretion

Change from baseline in urinary ellagitannin metabolite excretion after 12 weeks of intervention.

Full Information

NCT ID

NCT03000101

First Posted

December 19, 2016

Last Updated

August 29, 2023

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Collaborators

University of Bologna, Conserve Italia, GAT Foods

1. Study Identification

Unique Protocol Identification Number

NCT03000101

Brief Title

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

Acronym

POME2016

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 19, 2017 (Actual)

Primary Completion Date

July 19, 2023 (Actual)

Study Completion Date

December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Collaborators

University of Bologna, Conserve Italia, GAT Foods

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn's Disease, Ulcerative Colitis

Keywords

Biomarkers, Colitis, Colitis, Ulcerative, Colonic Diseases, Crohn Disease, Digestive System Diseases, Fruit, Fruit and Vegetable Juices, Gastroenteritis, Gastrointestinal Diseases, Humans, Hydrolysable Tannins, Inflammation, Inflammatory Bowel Disease, Intestinal Diseases, Punicaceae

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pomegranate juice

Arm Type

Experimental

Arm Description

The pomegranate juice is 100% pomegranate juice, not from concentrate.

Arm Title

Placebo beverage

Arm Type

Placebo Comparator

Arm Description

The placebo beverage consists in water added with sugar and citric acid.

Intervention Type

Other

Intervention Name(s)

100% pomegranate juice

Intervention Description

125 mL of 100% pomegranate juice twice daily for 12 weeks

Intervention Type

Other

Intervention Name(s)

placebo beverage

Intervention Description

125 mL of placebo beverage twice daily for 12 weeks

Primary Outcome Measure Information:

Title

Changes in fecal calprotectin

Description

Time Frame

Baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Changes in plasma concentration of ellagitannin metabolites

Description

Change from baseline in plasma concentration of ellagitannin metabolites after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

Title

Changes in circulating cytokines levels

Description

Change from baseline in plasma levels of cytokines after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

Title

Changes in circulating trimethylamine-N-oxide (TMAO) levels

Description

Change from baseline in plasma levels of TMAO after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

Title

Changes in gene expression levels in peripheral blood mononuclear cells (PBMC)

Description

Change from baseline in expression levels of selected genes in PBMC by qPCR after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

Title

Changes in gene expression levels in intestinal biopsies

Description

Change from baseline in expression levels of selected genes in intestinal biopsies by qPCR after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

Title

Changes in urinary ellagitannin metabolite excretion

Description

Change from baseline in urinary ellagitannin metabolite excretion after 12 weeks of intervention.

Time Frame

Baseline and 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francesca Danesi, PhD

Organizational Affiliation

Department of Agri-Food Sciences and Technologies, University of Bologna

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Luigi Ricciardiello, MD, Prof

Organizational Affiliation

Department of Medical and Surgical Sciences, University of Bologna

Official's Role

Principal Investigator

Facility Information:

Facility Name

U.O. Gastroenterologia - Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi

City

Bologna

ZIP/Postal Code

40138

Country

Italy

12. IPD Sharing Statement

Plan to Share IPD

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

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