Markers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach

NCT04513015 | Active Not Recruiting

• 1 other identifier: OxIBDiet-2020
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 2

Brief Summary

Inflammatory bowel disease (IBD), including Crohn's disease (CD), Ulcerative Colitis (UC) and IBD-unclassified (IBD-U) is a chronic inflammatory intestinal disorders that affect both children and adults. Patients with IBD can present with severe gastrointestinal symptoms, require frequent hospitalizations, expensive medical treatments and can develop invalidating complications requiring surgery. The incidence of IBD is increasing worldwide. The pathogenesis is multifactorial with immunological, environmental and genetic factors contributing to the disease. There is evidence that oxidative stress (OS) imbalance is involved in IBD onset and evolution, although the exact contribution to the pathogenes is unclear. An antioxidant dietetic approach is promising as an adjunctive treatment of IBD. The main aims of this project are to characterize the OS imbalance in IBD in relation to disease's features and to genetic factors and to evaluate the efficacy of an antioxidant dietetic treatment

Conditions

Inflammatory Bowel Diseases

Keywords

oxidative stress imbalance; antioxidant diet

Outcome Measures

Primary Outcomes (5)

• Blood levels of ROS and glutathione in patients with IBD and controls

  Blood levels of ROS will be determined by cytofluorimetry, blood levels of glutathione by spectrofluorimetry

  Baseline

• Total antioxidant capacity (Trolox equivalent and ferrous equivalent) in patients with IBD and controls

  Trolox equivalent will be assessed by antioxidant assay Kit, ferrous equivalent instead wille require a manual assessment.

  Baseline

• Antioxidant enzymes pattern (GST, SOD, GPxs, GR enzyme levels, activity and transcripts) in patients with IBD and controls

  Spectrophotometer will be used to assess enzyme levels and activity, cDNA kit to determine enzyme transcripts.

  Baseline

• Plasma hydroperoxides and thiobarbituric acid reactive species in patients with IBD and controls

  Plasma hydroperoxides will be detected by LPO ELISA kit, thiobarbituric acid reactive species by TBARS assay kit.

  Baseline

• Urine oxidized guanines (8-OHdG, 8-OHG e guanosine) levels in patients with IBD and controls

  DNA/RNA oxydate damage kit will be used to study urine oxidized guanines levels.

  Baseline

Secondary Outcomes (1)

• Polymorphisms of genes implicated in oxidative stress defense (SOD1, SOD2, SOD3; GPX1, GPX2, GPX3; GPX4; GPX5; GSTA1; GSTA2; GSTM1; GSTM2; GSTM3; GSTP1; GSTO1; NQ01 NQ02; NOX1; NOX3; NOX4 and NOX5 genes) in patients with IBD and controls

  Baseline

Other Outcomes (13)

• Blood levels of ROS and glutathione in patients with IBD after a specific antioxidant dietary treatment

  12 weeks

• Total antioxidant capacity (Trolox equivalent and ferrous equivalent) in patients with IBD after a specific antioxidant dietary treatment

  12 weeks

• Antioxidant enzymes pattern (GST, SOD, GPxs, GR enzyme levels, activity and transcripts) in patients with IBD after a specific antioxidant dietary treatment

  12 weeks

Study Arms (2)

Antioxidant diet

EXPERIMENTAL

Group Antioxidant diet will receive 8 weeks of antioxidant dietary treatment

Dietary Supplement: Antioxidant diet

Normal diet

ACTIVE COMPARATOR

Group Normal diet will continue a normal dietetic scheme (corresponding to a isocaloric, normolipidic diet for age and sex).

Dietary Supplement: Normal dietetic scheme

Interventions

Antioxidant diet DIETARY_SUPPLEMENT

The "antioxidant diet" will include the principal antioxidant molecules/nutrients previously shown to be beneficial in IBD: Flavonoids, particularly resveratrol and curcumin; Olive oil; Glutathione, Vitamins A, C, E; Carotenoids; Selenium and Omega 3 Fatty Acids (PUFAs). The daily amount of these substances will be calculated following the published evidence, whether these amounts will not be achievable by a standard diet, a supplementary formulation will be proposed.

Antioxidant diet

Normal dietetic scheme DIETARY_SUPPLEMENT

Isocaloric, normolipidic diet for age and sex

Normal diet

Eligibility Criteria

• Age: 6 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Diagnosis of IBD

You may not qualify if:

• permanent stoma
• cancer
• cardiovascular disease
• ischemic disease
• Alzheimer's disease
• type 2 diabetes

Sponsors & Collaborators

• Università Politecnica delle Marche: lead
• Ministry of Health, Italy: collaborator

Study Sites (2)

SOD Clinica Pediatrica, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60123, Italy

Location

SOD Clinica di Gastroenterologia, Epatologia ed Endoscopia Digestiva, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

Related Publications (11)

• Kolho KL, Ainamo A. Progress in the treatment and outcome of pediatric inflammatory bowel disease patients. Expert Rev Clin Immunol. 2016 Dec;12(12):1337-1345. doi: 10.1080/1744666X.2016.1201422. Epub 2016 Jun 29.

  PMID: 27322874 BACKGROUND

• Sigall-Boneh R, Levine A, Lomer M, Wierdsma N, Allan P, Fiorino G, Gatti S, Jonkers D, Kierkus J, Katsanos KH, Melgar S, Yuksel ES, Whelan K, Wine E, Gerasimidis K. Research Gaps in Diet and Nutrition in Inflammatory Bowel Disease. A Topical Review by D-ECCO Working Group [Dietitians of ECCO]. J Crohns Colitis. 2017 Dec 4;11(12):1407-1419. doi: 10.1093/ecco-jcc/jjx109.

  PMID: 28961811 BACKGROUND

• Gatti S, Galeazzi T, Franceschini E, Annibali R, Albano V, Verma AK, De Angelis M, Lionetti ME, Catassi C. Effects of the Exclusive Enteral Nutrition on the Microbiota Profile of Patients with Crohn's Disease: A Systematic Review. Nutrients. 2017 Aug 4;9(8):832. doi: 10.3390/nu9080832.

  PMID: 28777338 BACKGROUND

• Tian T, Wang Z, Zhang J. Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies. Oxid Med Cell Longev. 2017;2017:4535194. doi: 10.1155/2017/4535194. Epub 2017 Jun 28.

  PMID: 28744337 RESULT

• Pereira C, Gracio D, Teixeira JP, Magro F. Oxidative Stress and DNA Damage: Implications in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2015 Oct;21(10):2403-17. doi: 10.1097/MIB.0000000000000506.

  PMID: 26193347 RESULT

• Mrowicka M, Mrowicki J, Mik M, Wojtczak R, Dziki L, Dziki A, Majsterek I. Association between SOD1, CAT, GSHPX1 polymorphisms and the risk of inflammatory bowel disease in the Polish population. Oncotarget. 2017 Nov 27;8(65):109332-109339. doi: 10.18632/oncotarget.22675. eCollection 2017 Dec 12.

  PMID: 29312611 RESULT

• Kosaka T, Yoshino J, Inui K, Wakabayashi T, Kobayashi T, Watanabe S, Hayashi S, Hirokawa Y, Shiraishi T, Yamamoto T, Tsuji M, Katoh T, Watanabe M. Involvement of NAD(P)H:quinone oxidoreductase 1 and superoxide dismutase polymorphisms in ulcerative colitis. DNA Cell Biol. 2009 Dec;28(12):625-31. doi: 10.1089/dna.2009.0877.

  PMID: 19715479 RESULT

• Dryden GW, Lam A, Beatty K, Qazzaz HH, McClain CJ. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm Bowel Dis. 2013 Aug;19(9):1904-12. doi: 10.1097/MIB.0b013e31828f5198.

  PMID: 23846486 RESULT

• Kolacek M, Muchova J, Dvorakova M, Paduchova Z, Zitnanova I, Cierna I, Orszaghova Z, Szekyova D, Jajcaiova-Zednickova N, Kovacs L, Durackova Z. Effect of natural polyphenols (Pycnogenol) on oxidative stress markers in children suffering from Crohn's disease--a pilot study. Free Radic Res. 2013 Aug;47(8):624-34. doi: 10.3109/10715762.2013.807508. Epub 2013 Jun 13.

  PMID: 23710677 RESULT

• Rastegarpanah M, Malekzadeh R, Vahedi H, Mohammadi M, Elahi E, Chaharmahali M, Safarnavadeh T, Abdollahi M. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin J Integr Med. 2015 Dec;21(12):902-6. doi: 10.1007/s11655-012-1026-x. Epub 2012 Apr 11.

  PMID: 22528757 RESULT

• Aghdassi E, Wendland BE, Steinhart AH, Wolman SL, Jeejeebhoy K, Allard JP. Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial. Am J Gastroenterol. 2003 Feb;98(2):348-53. doi: 10.1111/j.1572-0241.2003.07226.x.

  PMID: 12591053 RESULT

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Carlo Catassi, Professor

  Università Politecnica delle Marche

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: IBD subjects (40 children and 40 adults, 50% with CD and 50% with UC) will be enrolled in different conditions: at diagnosis, in remission, at relapse. For each IBD subject an age and gender matched control subject will be enrolled (40 children and 40 adults). In a subgroup of subjects (20 children and 20 adults, 50% with CD and 50% with UC) in clinical remission/mild disease a dietetic approach will be proposed. Patients on steroids and patients with strictures will not be enrolled for this part of the study. Patients will be randomized in 2 groups: Group Antioxidant diet will receive 8 weeks of antioxidant dietary treatment and group Normal diet will continue a normal dietetic scheme (corresponding to a isocaloric, normolipidic diet for age and sex).

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 14, 2020
• Study Start: December 15, 2019
• Primary Completion: June 8, 2024
• Study Completion: December 8, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

Locations

IT (2)