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

NCT ID: NCT06525974

Last Updated: 2024-07-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2026-12-30

Brief Summary

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

Detailed Description

Ulcerative colitis (UC) is a sub-category of inflammatory bowel diseases (IBD) that causes mucosal inflammation in the rectum and lower colon. Although the exact pathogenesis of ulcerative colitis remains unclear, potential risk factors include altered immune responses, overactive immune response toward commensal microflora, genetic susceptibility, and environmental factors that have been considered as potential risk factors for UC .

The pathogenesis of UC consists of immuno-inflammatory pathways related to the multiple components of the intestine, including the epithelial barrier, dysregulation of immunological responses, leukocyte recruitment, and genetic factors. The understanding of immuno-inflammatory pathways of UC might lead to the development of a specific therapy and/or a novel treatment that could be more efficient .

Mesalazine (also known as mesalamine or 5- amino salicylic acid, 5-ASA) has a well-established role in UC management. It is the first line therapy for mild to moderate UC and it is considered the cornerstone in the management of UC. The mechanism of action of mesalazine is diverse. It acts locally on colonic mucosa and reduces inflammation by several anti-inflammatory processes .

Febuxostat (FXT) is a medication used in management hyperuricemia espicially in gout, a condition characterized by joints pain as result of deposition of uric acid crystals due to elevated urate blood levels. It's a non-purine selective xanthine oxidase inhibitor. Xanthin oxidase is an enzyme that plays a main role in production of uric acid from xanthine and hypoxanthine.

Furthermore, there is no need for dose modification of FXT in case of renal impairment and so it's great choice for many patients as it may exhibit renal protective effect and delay progression of kidney injury and according to Zhou H et al. FXT appears to be well tolerated in healthy population who has normal serum uric acid levels with no serious adverse events were reported .

Lately, febuxostat's spectrum of use has expanded over hyperuricemia management as result of it's ability of amelioration oxidative stress and regulation inflammatory response due to pro -inflammatory cytokines modulation.

Keyvan Amirshahrokhi and El-Mahdy NA et al. inspected the potential of FXT in mitigating ulcerative colitis in mice. The findings from those studies suggest that febuxostat may exert anti- inflammatory effects in the context of ulcerative colitis. Febuxostat's anti- inflammatory effects in ulcerative colitis may be linked to its inhibition of the nuclear factor kappa B (NF-κB) signaling pathway, a key regulator of inflammation. This inhibition can reduce the production of proinflammatory cytokines, contributing to its anti-inflammatory properties .

Although, preclinical studies in animal models are promising, translating these results into clinical applications is necessary to evaluate the safety and efficacy of FXT in managing UC in human.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Control group (Mesalamine group)

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

Group Type: ACTIVE_COMPARATOR

Mesalamine

Intervention Type: DRUG

1 g mesalamine three times daily for 3 months.

Experimental group (Febuxostat group)

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

Group Type: EXPERIMENTAL

Febuxostat

Intervention Type: DRUG

40mg of Febuxostat once daily

Interventions

Febuxostat

40mg of Febuxostat once daily

Intervention Type: DRUG

Mesalamine

1 g mesalamine three times daily for 3 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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.
• Patients were treated with mercaptopurine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Abdelrahman Mohammed El-kabbary Hasan Diab

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Abdelrahman Mohammed Elkabbary Hasan Diab

Role: CONTACT

alabbary99@gmail.com

01102400485 ext. 002

References

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Other Identifiers

MS.24.04.2758

Identifier Type: -

Identifier Source: org_study_id