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

NCT03000101 | Unknown

• 2 other identifiers: RBSI14LHMBSIR Programme no. RBSI14LHMB
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Changes in plasma concentration of ellagitannin metabolites

  Baseline and 12 weeks

• Changes in circulating cytokines levels

  Baseline and 12 weeks

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

  Baseline and 12 weeks

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

  Baseline and 12 weeks

• Changes in gene expression levels in intestinal biopsies

  Baseline and 12 weeks

Study Arms (2)

Pomegranate juice

EXPERIMENTAL

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

Other: 100% pomegranate juice

Placebo beverage

PLACEBO COMPARATOR

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

Other: placebo beverage

Interventions

100% pomegranate juice OTHER

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

Pomegranate juice

placebo beverage OTHER

125 mL of placebo beverage twice daily for 12 weeks

Placebo beverage

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead
• University of Bologna: collaborator
• Conserve Italia: collaborator
• GAT Foods: collaborator

Study Sites (1)

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

Bologna, 40138, Italy

Location

Related Publications (28)

• Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI). Gastroenterology. 1979 Oct;77(4 Pt 2):843-6.

  PMID: 467941 BACKGROUND

• Biasi F, Astegiano M, Maina M, Leonarduzzi G, Poli G. Polyphenol supplementation as a complementary medicinal approach to treating inflammatory bowel disease. Curr Med Chem. 2011;18(31):4851-65. doi: 10.2174/092986711797535263.

  PMID: 21919842 BACKGROUND

• Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, Ricchiuti A, Marchi S, Bottai M. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut. 2005 Mar;54(3):364-8. doi: 10.1136/gut.2004.043406.

  PMID: 15710984 BACKGROUND

• D'Inca R, Dal Pont E, Di Leo V, Ferronato A, Fries W, Vettorato MG, Martines D, Sturniolo GC. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis. 2007 Apr;22(4):429-37. doi: 10.1007/s00384-006-0159-9. Epub 2006 Jul 13.

  PMID: 16838143 BACKGROUND

• D'Amore S, Vacca M, Graziano G, D'Orazio A, Cariello M, Martelli N, Di Tullio G, Salvia R, Grandaliano G, Belfiore A, Pellegrini F, Palasciano G, Moschetta A. Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome. Biochim Biophys Acta. 2013 Dec;1832(12):2289-301. doi: 10.1016/j.bbadis.2013.09.006. Epub 2013 Sep 21.

  PMID: 24060638 BACKGROUND

• Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004 Oct;60(4):505-12. doi: 10.1016/s0016-5107(04)01878-4.

  PMID: 15472670 BACKGROUND

• D'Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, Geens P, Iwens D, Aerden I, Van Assche G, Van Olmen G, Rutgeerts P. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Dec;18(12):2218-24. doi: 10.1002/ibd.22917. Epub 2012 Feb 16.

  PMID: 22344983 BACKGROUND

• Espin JC, Gonzalez-Barrio R, Cerda B, Lopez-Bote C, Rey AI, Tomas-Barberan FA. Iberian pig as a model to clarify obscure points in the bioavailability and metabolism of ellagitannins in humans. J Agric Food Chem. 2007 Dec 12;55(25):10476-85. doi: 10.1021/jf0723864. Epub 2007 Nov 9.

  PMID: 17990850 BACKGROUND

• Foell D, Frosch M, Sorg C, Roth J. Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. Clin Chim Acta. 2004 Jun;344(1-2):37-51. doi: 10.1016/j.cccn.2004.02.023.

  PMID: 15149869 BACKGROUND

• Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Lofberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000 Sep;47(3):404-9. doi: 10.1136/gut.47.3.404.

  PMID: 10940279 BACKGROUND

• Gimenez-Bastida JA, Larrosa M, Gonzalez-Sarrias A, Tomas-Barberan F, Espin JC, Garcia-Conesa MT. Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts. J Agric Food Chem. 2012 Sep 12;60(36):8866-76. doi: 10.1021/jf300290f. Epub 2012 Apr 16.

  PMID: 22463485 BACKGROUND

• Larrosa M, Gonzalez-Sarrias A, Yanez-Gascon MJ, Selma MV, Azorin-Ortuno M, Toti S, Tomas-Barberan F, Dolara P, Espin JC. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J Nutr Biochem. 2010 Aug;21(8):717-25. doi: 10.1016/j.jnutbio.2009.04.012. Epub 2009 Jul 18.

  PMID: 19616930 BACKGROUND

• Marin M, Maria Giner R, Rios JL, Recio MC. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis. J Ethnopharmacol. 2013 Dec 12;150(3):925-34. doi: 10.1016/j.jep.2013.09.030. Epub 2013 Oct 17.

  PMID: 24140585 BACKGROUND

• Martin DA, Bolling BW. A review of the efficacy of dietary polyphenols in experimental models of inflammatory bowel diseases. Food Funct. 2015 Jun;6(6):1773-86. doi: 10.1039/c5fo00202h.

  PMID: 25986932 BACKGROUND

• Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, Nagy L. Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets. BMC Med Genomics. 2010 May 5;3:15. doi: 10.1186/1755-8794-3-15.

  PMID: 20444268 BACKGROUND

• Miller CA, Corbin KD, da Costa KA, Zhang S, Zhao X, Galanko JA, Blevins T, Bennett BJ, O'Connor A, Zeisel SH. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014 Sep;100(3):778-86. doi: 10.3945/ajcn.114.087692. Epub 2014 Jun 18.

  PMID: 24944063 BACKGROUND

• Pellegrini N, Salvatore S, Valtuena S, Bedogni G, Porrini M, Pala V, Del Rio D, Sieri S, Miglio C, Krogh V, Zavaroni I, Brighenti F. Development and validation of a food frequency questionnaire for the assessment of dietary total antioxidant capacity. J Nutr. 2007 Jan;137(1):93-8. doi: 10.1093/jn/137.1.93.

  PMID: 17182807 BACKGROUND

• Rosillo MA, Sanchez-Hidalgo M, Cardeno A, de la Lastra CA. Protective effect of ellagic acid, a natural polyphenolic compound, in a murine model of Crohn's disease. Biochem Pharmacol. 2011 Oct 1;82(7):737-45. doi: 10.1016/j.bcp.2011.06.043. Epub 2011 Jul 7.

  PMID: 21763290 BACKGROUND

• Rosillo MA, Sanchez-Hidalgo M, Cardeno A, Aparicio-Soto M, Sanchez-Fidalgo S, Villegas I, de la Lastra CA. Dietary supplementation of an ellagic acid-enriched pomegranate extract attenuates chronic colonic inflammation in rats. Pharmacol Res. 2012 Sep;66(3):235-42. doi: 10.1016/j.phrs.2012.05.006. Epub 2012 Jun 4.

  PMID: 22677088 BACKGROUND

• Schoepfer AM, Trummler M, Seeholzer P, Seibold-Schmid B, Seibold F. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis. 2008 Jan;14(1):32-9. doi: 10.1002/ibd.20275.

  PMID: 17924558 BACKGROUND

• Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. doi: 10.1056/NEJM198712243172603.

  PMID: 3317057 BACKGROUND

• Snyder SM, Reber JD, Freeman BL, Orgad K, Eggett DL, Parker TL. Controlling for sugar and ascorbic acid, a mixture of flavonoids matching navel oranges significantly increases human postprandial serum antioxidant capacity. Nutr Res. 2011 Jul;31(7):519-26. doi: 10.1016/j.nutres.2011.06.006.

  PMID: 21840468 BACKGROUND

• Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000 Jul;119(1):15-22. doi: 10.1053/gast.2000.8523.

  PMID: 10889150 BACKGROUND

• Valerii MC, Ricci C, Spisni E, Di Silvestro R, De Fazio L, Cavazza E, Lanzini A, Campieri M, Dalpiaz A, Pavan B, Volta U, Dinelli G. Responses of peripheral blood mononucleated cells from non-celiac gluten sensitive patients to various cereal sources. Food Chem. 2015 Jun 1;176:167-74. doi: 10.1016/j.foodchem.2014.12.061. Epub 2014 Dec 23.

  PMID: 25624220 BACKGROUND

• Walmsley RS, Ayres RC, Pounder RE, Allan RN. A simple clinical colitis activity index. Gut. 1998 Jul;43(1):29-32. doi: 10.1136/gut.43.1.29.

  PMID: 9771402 BACKGROUND

• Wilson A, Teft WA, Morse BL, Choi YH, Woolsey S, DeGorter MK, Hegele RA, Tirona RG, Kim RB. Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease. Dig Dis Sci. 2015 Dec;60(12):3620-30. doi: 10.1007/s10620-015-3797-3. Epub 2015 Jul 10.

  PMID: 26160437 BACKGROUND

• Scaioli E, Belluzzi A, Ricciardiello L, Del Rio D, Rotondo E, Mena P, Derlindati E, Danesi F. Pomegranate juice to reduce fecal calprotectin levels in inflammatory bowel disease patients with a high risk of clinical relapse: Study protocol for a randomized controlled trial. Trials. 2019 Jun 6;20(1):327. doi: 10.1186/s13063-019-3321-8.

  PMID: 31171016 RESULT

• Minato I, Mena P, Ricciardiello L, Scaioli E, Belluzzi A, Rotondo E, Derlindati E, Montanini B, Michelini C, Tosi N, Agullo Garcia V, Picone G, Mengucci C, Dobani S, Salamanca P, Rosi A, Dall'Asta M, Bresciani L, Curti C, Spisni E, Dei Cas A, Bordoni A, Tomas-Barberan FA, Ferguson LR, Del Rio D, Danesi F. Evidence for a Modulatory Effect of a 12-Week Pomegranate Juice Intervention on the Transcriptional Response in Inflammatory Bowel Disease Patients Reducing Fecal Calprotectin Levels: Findings From a Proof-of-Principle Study. Mol Nutr Food Res. 2025 Aug;69(15):e70067. doi: 10.1002/mnfr.70067. Epub 2025 Apr 21.

  PMID: 40255128 DERIVED

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative; Colitis; Colonic Diseases; Digestive System Diseases; Gastroenteritis; Gastrointestinal Diseases; Inflammation; Inflammatory Bowel Diseases; Intestinal Diseases

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Francesca Danesi, PhD

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

  STUDY DIRECTOR

• Luigi Ricciardiello, MD, Prof

  Department of Medical and Surgical Sciences, University of Bologna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Andrea Belluzzi, MD PhD

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 21, 2016
• Study Start: January 19, 2017
• Primary Completion: July 19, 2023
• Study Completion: December 29, 2023
• Last Updated: August 30, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)