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

Drug Des Devel Ther. 2024 Nov 16:18:5239-5253. doi: 10.2147/DDDT.S490772. eCollection 2024.

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: Fenofibrate; Mesalamine; NLRP3/AMPK; PPARα; Ulcerative colitis.

Publication types

  • Randomized Controlled Trial
  • Case Reports
  • Clinical Trial

MeSH terms

  • AMP-Activated Protein Kinases* / metabolism
  • Adult
  • Colitis, Ulcerative* / drug therapy
  • Female
  • Fenofibrate* / administration & dosage
  • Fenofibrate* / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Male
  • Mesalamine / administration & dosage
  • Mesalamine / pharmacology
  • Mesalamine / therapeutic use
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein* / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • PPAR alpha / agonists
  • PPAR alpha / metabolism
  • Pilot Projects
  • Sirtuin 1* / metabolism
  • Young Adult

Substances

  • Fenofibrate
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Sirtuin 1
  • AMP-Activated Protein Kinases
  • NLRP3 protein, human
  • SIRT1 protein, human
  • Mesalamine
  • PPAR alpha

Associated data

  • ClinicalTrials.gov/NCT05781698

Grants and funding

There is no funding to report.