Fenofibrate As an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation Via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2024 Nov 22

PMID 39575188

Authors

Sumaiah J Alarfaj

Mostafa M Bahaa

Thanaa A Elmasry

Eman I Elberri

Eman El-Khateeb

Amir O Hamouda

Muhammed M Salahuddin

Marwa Kamal

Abdel-Naser Abdel-Atty Gadallah

Nashwa Eltantawy

Mohamed Yasser

Walaa A Negm

Manal A Hamouda

Amsha S Alsegiani

Sarah Alrubia

Mamdouh Eldesoqui

Mahmoud S Abdallah

Affiliations

Soon will be listed here.

Abstract

Background: Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.

Aim: The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.

Methods: A total of 70 patients with mild to moderate UC were allocated randomly and assigned to two groups (n = 35 each) from Gastroenterology Department, Faculty of Medicine, Menoufia University. The mesalamine group received a placebo along with 1 g of mesalamine three times daily, while the fenofibrate group received 1 g of mesalamine three times and fenofibrate 160 mg once daily. The study duration was for six months. A gastroenterologist assessed patients by non-invasive Partial Mayo Score (PMS) and the Inflammatory Bowel Disease Questionnaire (IBDQ) to evaluate clinical response and remission. The serum levels of silent information regulator 1 (SIRT1), NOD-like receptor protein 3 (NLRP3), and adenosine monophosphate activated protein kinase (AMPK), as well as fecal calprotectin levels were examined to determine the biological effect of fenofibrate.

Results: After treatment, the fenofibrate group showed statistically significant reductions in PMS ( 0.044) and improved digestive domain of IBDQ ( 0.023). Additionally, there were significant decreases in serum NLRP3 ( 0.041) and fecal calprotectin ( 0.035), along with significant increases in SIRT1 ( 0.002) and AMPK ( 0.0003). The fenofibrate group also had higher response and remission rates compared to the mesalamine group.

Conclusion: Fenofibrate may be a promising adjunct for improving clinical outcomes, quality of life, and modulating inflammation in mild to moderate patients with UC.

Trial Registration Identifier: NCT05781698.

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