- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04513015
Markers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach (OxIBDiet)
Markers of Oxidative Stress in Inflammatory Bowel Disease in Children and Adults: Risk Factors and Implications for a Dietetic Approach
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
IBD is a complex disorder that is thought to be the result of an aberrant immune response to commensal bacteria in a genetically susceptible host. The chronic inflammation along the gastrointestinal tract that characterizes IBD results from an imbalance of effector lymphocytes and pro-inflammatory cytokines. Some of the cytokines, as well as the triggered leukocytes and activated macrophages, can produce large amounts of reactive oxygen species (ROS) thus predisposing to oxidative stress disturbances. Many of the clinical and pathophysiological features of IBD, particularly tissue injury (mucosal erosions) and fibrosis have been associated to redox imbalance due to continuous ROS production and a net decrease of antioxidant molecules. Although uncontrolled oxidative stress is destructive in inflammatory conditions, the body's antioxidant defenses can counteract the effects caused by excess of ROS. Antioxidants are protective molecules/compounds toward pro-oxidant molecules. They can be endogenous or/and come from the diet. Endogenous compounds include intracellular enzymatic antioxidants such as superoxide dismutases (SODs), glutathione peroxidase (GPX), and catalase (CAT), intracellular nonenzymatic antioxidant such as glutathione (GSH) and extracellular antioxidants such as vitamins (Vit. A-C-E-B group). GSH is considered the major non-protein low molecular weight defender against oxidative (or redox) stress and the most important cellular thiol buffer. Moreover it acts as cofactor for the antioxidant enzymes GPxs and GST. GSH has been used as a biomarker for inflammation and several studies showed reduced levels of GSH in inflammatory conditions. Experimental colitis models showed decreased GSH levels that can be restored to a normal level by antioxidants supplementation. Also antioxidant enzymes as SODs, CAT and GPxs were found dysregulated in IBD condition. The differences in the regulation of expression of SOD, CAT and GPxs may not only reflect their importance in physiology, but may be also insufficient in removal of ROS under inflammatory conditions such as IBD.
Recently an association between SOD1, CAT and GSHPX1 polymorphisms and the risk of inflammatory bowel disease in the Polish population has been described. Kosaka et al. found a correlation between age of onset and severity of IBD with polymorphisms in SOD2 manganese superoxide dismutase and NAD(P)H quinone oxidoreductase. In this respect, IBD disease can be regarded as multifactorial disease. There are several lines of evidence to suggest that diet is a key player in the onset, perpetuation and management of IBD. The most important evidence linking diet to IBD comes from exclusive enteral nutrition (EEN) that is the primary induction treatment of active paediatric Crohn Disease (CD). Epidemiological evidence associates certain dietary nutrients and components to the increased risk of IBD. There is emerging evidence that some diets, including the Specific Carbohydrate Diet (SCD) and the CD Exclusion Diet (CDED) could treat or prevent subsequent disease flare. Data previously presented induce to the hypothesis that an antioxidant dietetic approach, could have a role in the treatment of IBD. Dietary antioxidants may include ascorbic acid, vitamin E, glutathione, methionine, carotenoids, polyphenolic compounds, selenium and vitamin A. Clinical experience evaluating antioxidant dietetic approach in IBD patients is limited to few studies, mostly investigating the effects of single antioxidants in small number of patients. So far pediatric data regarding the oxidative status in children with IBD have rarely been reported. Collecting data in IBD children and comparing these with adults data, particularly in subjects at diagnosis, would give the unique opportunity to evaluate the role of oxidative stress in IBD pathogenesis. OxIBDiet working hypothesis is that oxidative stress imbalance is a key feature of IBD and the persistence of such imbalance is likely to contribute to the development of complications and more broadly to the evolution of the disease. A comparison between oxidative stress imbalance in children and adults with IBD and controls will address the question whether the stress imbalance is a consequence or a primary event in the inflammatory burden of IBD. Addressing these pathways and targeting the oxidative damage can have potential implications in IBD monitoring and treatment.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Carlo Catassi, Professor
- Phone Number: 00390715962114
- Email: c.catassi@staff.univpm.it
Study Contact Backup
- Name: Simona Gatti, M.D.
- Phone Number: 00390715962114
- Email: simona.gatti@hotmail.it
Study Locations
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-
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Ancona, Italy, 60123
- Recruiting
- SOD Clinica Pediatrica, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
-
Contact:
- Carlo Catassi, Professor
- Phone Number: 00390715962114
- Email: c.catassi@staff.univpm.it
-
Contact:
- Simona Gatti, M.D.
- Phone Number: 00390715962114
- Email: simona.gatti@hotmail.it
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Ancona, Italy, 60126
- Recruiting
- SOD Clinica di Gastroenterologia, Epatologia ed Endoscopia Digestiva, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
-
Contact:
- Antonio Di Sario, M.D:
- Phone Number: 00390715964678
- Email: ibdunit.clgastroancona@gmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Diagnosis of IBD
Exclusion Criteria:
- permanent stoma
- cancer
- cardiovascular disease
- ischemic disease
- Alzheimer's disease
- type 2 diabetes
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Antioxidant diet
Group Antioxidant diet will receive 8 weeks of antioxidant dietary treatment
|
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.
|
Active Comparator: Normal diet
Group Normal diet will continue a normal dietetic scheme (corresponding to a isocaloric, normolipidic diet for age and sex).
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Isocaloric, normolipidic diet for age and sex
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood levels of ROS and glutathione in patients with IBD and controls
Time Frame: Baseline
|
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
Time Frame: Baseline
|
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
Time Frame: Baseline
|
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
Time Frame: Baseline
|
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
Time Frame: Baseline
|
DNA/RNA oxydate damage kit will be used to study urine oxidized guanines levels.
|
Baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
Time Frame: Baseline
|
Genetic polymorphisms will be studied by next generation sequencing
|
Baseline
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood levels of ROS and glutathione in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Blood levels of ROS will be determined by cytofluorimetry, blood levels of glutathione by spectrofluorimetry at baseline and after 12 weeks of dietary treatment.
|
12 weeks
|
Total antioxidant capacity (Trolox equivalent and ferrous equivalent) in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Trolox equivalent will be assessed by antioxidant assay Kit, ferrous equivalent instead wille require a manual assessment at baseline and after 12 weeks of 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
Time Frame: 12 weeks
|
Spectrophotometer will be used to assess enzyme levels and activity, cDNA kit to determine enzyme transcripts at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Plasma hydroperoxides and thiobarbituric acid reactive species in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Plasma hydroperoxides will be detected by LPO ELISA kit, thiobarbituric acid reactive species by TBARS assay kit at baseline and after 12 weeks of dietary treatment.
|
12 weeks
|
Urine oxidized guanines (8-OHdG, 8-OHG e guanosine) levels in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
DNA/RNA oxydate damage kit will be used to study urine oxidized guanines levels at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
PUCAI in pediatric patients with RCU after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
PUCAI score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
PCDAI in pediatric patients with CD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
PCDAI score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Phisician Global Assessment (PGA) score in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
PGA score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Calprotectin levels in patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Calprotectin levels will be analyzed in stool samples collected at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Harvey-Bradshaw score in adult patients with CD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Harvey-Bradshaw score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Mayo score in adult patients with RCU after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
Mayo score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
PedQoL score in pediatric patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
PedQoL score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
QoL score in adult patients with IBD after a specific antioxidant dietary treatment
Time Frame: 12 weeks
|
QoL score will be recorded at baseline and after 12 weeks of dietary treatment
|
12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Carlo Catassi, Professor, Università Politecnica delle Marche
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OxIBDiet-2020
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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