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

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 ( p = 0.044) and improved digestive domain of IBDQ ( p = 0.023). Additionally, there were significant decreases in serum NLRP3 ( p = 0.041) and fecal calprotectin ( p = 0.035), along with significant increases in SIRT1 ( p = 0.002) and AMPK ( p = 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. Keywords: Ulcerative colitis, Fenofibrate, Mesalamine, NLRP3/AMPK, PPARα