GPX4 Expression After Kono-S vs Conventional Anastomosis

NCT07772037 | Not Yet Recruiting

• 1 other identifier: S2026/SURG/01
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Crohn's disease is a long-term condition that causes inflammation in the bowel. Many people with Crohn's will need surgery at some point to remove damaged sections of intestine. Although surgery can improve symptoms, the disease often comes back near the join (anastomosis) where the bowel has been reconnected. Surgeons use different techniques to reconnect the bowel. One newer approach, called the Kono-S anastomosis, is designed to reduce the risk of Crohn's disease returning. Early results are promising, but it is still not fully understood why it may work better than traditional methods. This project aims to explore how the bowel heals after surgery by looking at oxidative stress, a type of tissue damage caused by an imbalance of harmful molecules in the body. The investigators will focus on a protective protein called glutathione peroxidase-4 (GPX4), an anti-oxidative enzyme that reduces oxidized phospholipids in biomembranes. By analysing tissue samples taken before and after surgery, the investigators will compare patients who had the Kono-S technique with those who had standard surgical joins. The investigators want to see whether differences in healing at a microscopic level could explain why some patients do better than others. The findings from this study could:

• Improve understanding of why Crohn's disease comes back after surgery.
• Help surgeons choose the best technique for each patient.
• Support the development of new treatments aimed at improving healing. Ultimately, this research aims to reduce the risk of disease recurrence and improve long-term outcomes for people living with Crohn's disease.

Conditions

Chrohn's Disease

Keywords

anastomotic healing,; GPX4

Outcome Measures

Primary Outcomes (1)

• • Difference in epithelial GPX4 expression score between Kono-S and conventional groups at the anastomotic site 6-12 months after IC resection.

  • Difference in epithelial GPX4 expression score between Kono-S and conventional groups at the anastomotic site 6-12 months after IC resection. The scale consists of n- not detected ( high reoccurrence risk) l- low level (high reoccurrence risk) m-medium level (low reoccurrence risk) h-high level (low reoccurrence risk)

  6-12 months after IC resection.

Secondary Outcomes (3)

• • Association between GPX4 expression and Rutgeerts score / endoscopic recurrence

  6-12 months after IC resection

• • Within patient change in GPX4 across pre-operative, operative and follow up tissues

  6-12 months after IC resection

• • Association between GPX4 and histological inflammation, fibrosis/stricture phenotype, or restenosis.

  6-12 months after IC resection

Study Arms (2)

Kono_S

Kono\_S anastomotic technique after following ileocolic resection for Crohn's disease

Conventional

conventional anastomotic techniques following ileocolic resection for Crohn's disease

Eligibility Criteria

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

Study Population

Crohn's disease undergoing ileocolic resection, for whom suitable archived histopathology material and relevant clinical data are available.

You may qualify if:

• Documented anastomotic configuration (Kono-S or conventional).
• Availability of archived pathology material from the resection specimen containing the anastomotic site.
• At least one additional tissue timepoint available: preoperative endoscopic biopsy or follow up endoscopic biopsy within 24 months.
• Available postoperative endoscopic follow up data (Rutgeerts score) where applicable.

You may not qualify if:

• Indeterminate colitis or non-Crohn's pathology on histology.
• Lack of retrievable tissue or poor tissue quality (e.g., extensive necrosis or autolysis) precluding IHC.
• Unclear anastomotic type.
• Absence of epithelial component in the available tissue (e.g., only serosa or fibrofatty tissue).
• Major confounders that could affect GPX4 expression, such as severe ischaemia, uncontrolled sepsis, or immediate reoperation at the anastomotic site.
• Patients with permanent stomas and no anastomotic follow up where interpretation would be ambiguous.

Sponsors & Collaborators

• East Kent Hospitals University NHS Foundation Trust: lead

Study Sites (1)

Queen Elizabeth the Queen Mother Hospital

Margate, Kent, CT9 4AN, United Kingdom

Location

Related Publications (6)

• Cathomas M, Saad B, Taha-Mehlitz S, Vankayalapati DK, Ghazal NE, Mourad MM, Ortlieb N, Than CA, Burri E, Glaser C, Heigl A, Neumann K, Honaker MD, Taha A, Rosenberg R. Safety and effectivity of Kono-S anastomosis in Crohn's patients: a systematic review and Meta-analysis. Langenbecks Arch Surg. 2024 Jul 22;409(1):227. doi: 10.1007/s00423-024-03412-x.

  PMID: 39037448 BACKGROUND

• Ye Y, Liu L, Jing Y, Yao S, Yang M, Dai X, Piao M, Xu X, Feng Z, Wang X, Liu Y, Miao J, Gao X, Yu Q, Cao X. Ferroptosis: A therapeutic opportunity of inflammatory bowel disease. Chin Med J (Engl). 2024 Apr 5;137(7):874-876. doi: 10.1097/CM9.0000000000002998. Epub 2024 Feb 23. No abstract available.

  PMID: 38391159 BACKGROUND

• Ioannidis M, Tjepkema J, Uitbeijerse MRP, van den Bogaart G. Immunomodulatory effects of 4-hydroxynonenal. Redox Biol. 2025 Sep;85:103719. doi: 10.1016/j.redox.2025.103719. Epub 2025 Jun 6.

  PMID: 40489926 BACKGROUND

• Ma K, Gu T, Wu Z, Li Z. Mechanisms of anastomotic leakage in colorectal cancer surgery: unraveling the roles of inflammation, immunity, and microbiota - a narrative review. Int J Surg. 2025 Dec 1;111(12):9482-9495. doi: 10.1097/JS9.0000000000003151. Epub 2025 Aug 6.

  PMID: 40773274 BACKGROUND

• Requena JR, Fu MX, Ahmed MU, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. Biochem J. 1997 Feb 15;322 ( Pt 1)(Pt 1):317-25. doi: 10.1042/bj3220317.

  PMID: 9078279 BACKGROUND

• Nos P, Domenech E. Postoperative Crohn's disease recurrence: a practical approach. World J Gastroenterol. 2008 Sep 28;14(36):5540-8. doi: 10.3748/wjg.14.5540.

  PMID: 18810773 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

including pre-operative mucosa, resection specimens, and postoperative endoscopic biopsies

Study Officials

• Caroline Cowley

  East Kent Hospitals University Foundation Trust

  STUDY CHAIR

Central Study Contacts

Giuseppe Preziosi, MD

CONTACT

+ 44 1843 225544.; g.preziosi@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: August 19, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: August 19, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)