Clinical Study to Evaluate the Possible Efficacy and Safety of Febuxostat in Patients With Ulcerative Colitis Treated With Mesalamine

NCT06525974 | Not Yet Recruiting Early Phase 1

• 1 other identifier: MS.24.04.2758
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluation the possible efficacy and safety of febuxostat in patients with ulcerative colitis treated with mesalamine.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Febuxostat; Mesalamine

Outcome Measures

Primary Outcomes (2)

• Assessment of disease activity using Partial Mayo Scoring Index (PMSI) assessment for Ulcerative Colitis Activity.

  It depends on three items: stool frequency, rectal bleeding (blood in stool) and Physician's Global Assessment. Each item has a score from 0 to 3 and total PMSI is the sum of scores for the three items.

  3 months

• Health-related quality of life (HRQOL) using the short inflammatory bowel disease questionnaire .

  Short Inflammatory Bowel Disease Ques-tionnaire (SIBDQ) version became widely known and is currently used worldwide both in clinical practice and clinical research. SIBDQ comprises a total of 10 questions grouped into four different dimensions: social, bowel, emotional, and systemic \[6, 7\]. Each question is scored by a 7-point Likert scale, ranging from 1 (a severe problem) to 7 (not a problem at all), giving an absolute SIBDQ score ranging from 10 (poor HRQoL) to 70 (opti-mal HRQoL). A SIBDQ score below 50 was considered as poor QoL.there are no validated cut-offs for the dif-ferent dimensions' scores. Hence, higher scores indicate a better HRQoL concerning that specific domain.Although patient-reported outcomes are highly valu-able for better patient care, patient responses to HRQoL instruments can be impacted by underlying cultural trends

  3 months

Study Arms (2)

Control group (Mesalamine group)

ACTIVE COMPARATOR

Control group (Mesalamine group, n =23) who will receive 1 g mesalamine three times daily for 3 months.

Drug: Mesalamine

Experimental group (Febuxostat group)

EXPERIMENTAL

Experimental group (Febuxostat group, n = 23) which will receive the standard treatment for UC plus 40 mg febuxostat once daily for 3 months.

Drug: Febuxostat

Interventions

Febuxostat DRUG

40mg of Febuxostat once daily

Experimental group (Febuxostat group)

Mesalamine DRUG

1 g mesalamine three times daily for 3 months.

Control group (Mesalamine group)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Both male and female will be included.
• Mild and moderate UC patients diagnosed and confirmed by endoscope.
• Patient treated with 5-aminosalislic acid (mesalamine).

You may not qualify if:

• Patients with severe UC.
• Significant liver and kidney function abnormalities.
• Diabetic patients.
• Patients with Colorectal cancer patients.
• Patients taking rectal or systemic steroids.
• Patients on immunosuppressants or biological therapies.
• Addiction to alcohol and / or drugs.
• Known allergy to the studied medications.
• History of complete or partial colectomy.
• Patients with congestive heart failure, other heart disease (Arrhythmia, ischemic heart disease including angina and myocardial infarction).
• Patients with other inflammatory diseases and active infection.
• Patients with stressful condition (COPD, morbid obesity).
• Patients with liver disease.
• Patients with thrombocytopenia and neutropenia.
• Pregnant or lactating females.

Sponsors & Collaborators

• Tanta University: lead

Related Publications (17)

• Abdel-Wahab BA, El-Shoura EAM, Shafiuddin Habeeb M, Zafaar D. Febuxostat alleviates Arsenic Trioxide-Induced renal injury in Rats: Insights on the crosstalk between NLRP3/TLR4, Sirt-1/NF-kappaB/TGF-beta signaling Pathways, and miR-23b-3p, miR-181a-5b expression. Biochem Pharmacol. 2023 Oct;216:115794. doi: 10.1016/j.bcp.2023.115794. Epub 2023 Sep 7.

  PMID: 37689273 BACKGROUND

• Amirshahrokhi K. Febuxostat attenuates ulcerative colitis by the inhibition of NF-kappaB, proinflammatory cytokines, and oxidative stress in mice. Int Immunopharmacol. 2019 Nov;76:105884. doi: 10.1016/j.intimp.2019.105884. Epub 2019 Sep 6.

  PMID: 31499267 BACKGROUND

• Cicero AFG, Fogacci F, Kuwabara M, Borghi C. Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update. Medicina (Kaunas). 2021 Jan 10;57(1):58. doi: 10.3390/medicina57010058.

  PMID: 33435164 BACKGROUND

• El-Mahdy NA, Saleh DA, Amer MS, Abu-Risha SE. Role of allopurinol and febuxostat in the amelioration of dextran-induced colitis in rats. Eur J Pharm Sci. 2020 Jan 1;141:105116. doi: 10.1016/j.ejps.2019.105116. Epub 2019 Oct 23.

  PMID: 31654756 BACKGROUND

• Elsisi AEE, Sokar SS, Shalaby MF, Abu-Risha SE. Nephroprotective effects of febuxostat and/or mirtazapine against gentamicin-induced nephrotoxicity through modulation of ERK 1/2, NF-kappaB and MCP1. Expert Rev Clin Pharmacol. 2021 Aug;14(8):1039-1050. doi: 10.1080/17512433.2021.1933435. Epub 2021 Jun 9.

  PMID: 34030558 BACKGROUND

• Fukui T, Maruyama M, Yamauchi K, Yoshitaka S, Yasuda T, Abe Y. Effects of Febuxostat on Oxidative Stress. Clin Ther. 2015 Jul 1;37(7):1396-401. doi: 10.1016/j.clinthera.2015.03.026. Epub 2015 Apr 23.

  PMID: 25913922 BACKGROUND

• Hao G, Duan W, Sun J, Liu J, Peng B. Effects of febuxostat on serum cytokines IL-1, IL-4, IL-6, IL-8, TNF-alpha and COX-2. Exp Ther Med. 2019 Jan;17(1):812-816. doi: 10.3892/etm.2018.6972. Epub 2018 Nov 15.

  PMID: 30651867 BACKGROUND

• Irvine EJ, Zhou Q, Thompson AK. The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996 Aug;91(8):1571-8.

  PMID: 8759664 BACKGROUND

• Kanji T, Gandhi M, Clase CM, Yang R. Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2015 Apr 19;16:58. doi: 10.1186/s12882-015-0047-z.

  PMID: 25928556 BACKGROUND

• Kim YE, Ahn SM, Oh JS, Kim YG, Lee CK, Yoo B, Hong S. Febuxostat dose requirement according to renal function in patients who achieve target serum urate levels: A retrospective cohort study. Joint Bone Spine. 2024 Mar;91(2):105668. doi: 10.1016/j.jbspin.2023.105668. Epub 2023 Nov 29.

  PMID: 38036062 BACKGROUND

• Kobayashi T, Siegmund B, Le Berre C, Wei SC, Ferrante M, Shen B, Bernstein CN, Danese S, Peyrin-Biroulet L, Hibi T. Ulcerative colitis. Nat Rev Dis Primers. 2020 Sep 10;6(1):74. doi: 10.1038/s41572-020-0205-x.

  PMID: 32913180 BACKGROUND

• Sarhan II, Abdellatif YA, Saad RE, Teama NM. Renoprotective effect of febuxostat on contrast-induced acute kidney injury in chronic kidney disease patients stage 3: randomized controlled trial. BMC Nephrol. 2023 Mar 22;24(1):65. doi: 10.1186/s12882-023-03114-4.

  PMID: 36949408 BACKGROUND

• Sloka J, Madej M, Strzalka-Mrozik B. Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules. 2023 Jun 29;28(13):5081. doi: 10.3390/molecules28135081.

  PMID: 37446747 BACKGROUND

• Solitano V, D'Amico F, Fiorino G, Paridaens K, Peyrin-Biroulet L, Danese S. Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis. J Clin Med. 2020 Sep 8;9(9):2905. doi: 10.3390/jcm9092905.

  PMID: 32911840 BACKGROUND

• Sturm A, Maaser C, Calabrese E, Annese V, Fiorino G, Kucharzik T, Vavricka SR, Verstockt B, van Rheenen P, Tolan D, Taylor SA, Rimola J, Rieder F, Limdi JK, Laghi A, Krustins E, Kotze PG, Kopylov U, Katsanos K, Halligan S, Gordon H, Gonzalez Lama Y, Ellul P, Eliakim R, Castiglione F, Burisch J, Borralho Nunes P, Bettenworth D, Baumgart DC, Stoker J; European Crohn's and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohns Colitis. 2019 Mar 26;13(3):273-284. doi: 10.1093/ecco-jcc/jjy114. No abstract available.

  PMID: 30137278 BACKGROUND

• Tatiya-Aphiradee N, Chatuphonprasert W, Jarukamjorn K. Immune response and inflammatory pathway of ulcerative colitis. J Basic Clin Physiol Pharmacol. 2018 Dec 19;30(1):1-10. doi: 10.1515/jbcpp-2018-0036.

  PMID: 30063466 BACKGROUND

• Zhou H, Zheng Y, Wu G, Hu X, Zhai Y, Iv D, Liu J, Wu L, Shentu J. Pharmacokinetics and tolerability of febuxostat after oral administration in healthy Chinese volunteers: a randomized, open-label, singleand multiple-dose three-way crossover study. Int J Clin Pharmacol Ther. 2016 Feb;54(2):115-24. doi: 10.5414/CP202394.

  PMID: 26636422 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Febuxostat; Mesalamine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Central Study Contacts

Abdelrahman Mohammed Elkabbary Hasan Diab

CONTACT

01102400485; alabbary99@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 29, 2024
• First Posted: July 29, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 29, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share