Chrohn's DiseaseNCT07772037
GPX4 Expression After Kono-S vs Conventional Anastomosis
An observational study of Chrohn's Disease, run by East Kent Hospitals University NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chrohn's Disease
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2026to Nov 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Crohn's disease undergoing ileocolic resection, for whom suitable archived histopathology material and relevant clinical data are available.
Who may be able to join
None listed.
Who cannot join
- • 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
Queen Elizabeth the Queen Mother Hospital
Margate, Kent, CT9 4AN
Giuseppe Preziosi, MD, +44 1843 225544., g.preziosi@nhs.net
Giuseppe Preziosi, MD
About this study
Official title: Oxidative Epithelial Injury After Ileocolic Resection a Retrospective Pilot Study Comparing Kono-S Versus Conventional Anastomotic Configurations Using Intestinal Epithelial GPX4 Expression.
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.
Read more
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.
Read the detailed description
Postoperative recurrence of Crohn's disease frequently occurs at or near the ileocolic anastomosis.1 Increasing evidence suggests that oxidative stress plays a central role in anastomotic healing, fibrosis and mucosal recurrence. Surgical injury triggers neutrophil recruitment and reactive oxygen species (ROS) production, which can initiate lipid peroxidation within intestinal epithelial membranes.3 Lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) activate inflammatory and fibrotic signalling pathways including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and transforming growth factor- β (TGF-β).2,4 GPX4 is a key antioxidant enzyme that detoxifies lipid peroxides and prevents ferroptosis, a regulated form of oxidative cell death.5 Reduced GPX4 activity has been described in inflammatory bowel disease and may contribute to epithelial injury and disease progression.5 Recent results have demonstrated that a reduced GPX4 expression at time of surgery predicts disease recurrence after ileocolonic resection independent of established clinical risk factors (e.g., smoking, penetrating disease, sex and age). Despite the recognised importance of oxidative stress in intestinal inflammation, its role at the surgical anastomosis in Crohn's disease has not been directly studied.
The Kono-S anastomosis is a functional end-to-end, antimesenteric configuration designed to reduce luminal distortion and faecal stasis while excluding mesenteric inflammatory influence. Early studies suggested reduced endoscopic recurrence compared with conventional anastomoses, although long-term clinical results remain mixed.6 The biological mechanisms underlying any benefit remain poorly understood.
The investigators hypothesise that the Kono-S anastomotic configuration may reduce local oxidative stress at the anastomotic site by limiting reactive oxygen species exposure and subsequent lipid peroxidation, as reflected by lower levels of markers such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) compared with conventional techniques. This more favourable redox environment may support preservation of epithelial antioxidant defence mechanisms, including maintenance of glutathione peroxidase-4 (GPX4) expression and activity, thereby reducing susceptibility of intestinal epithelial cells to ferroptosis. In turn, reduced lipid peroxidation may attenuate activation of key pro-inflammatory and pro-fibrotic signalling pathways, including MAPK, NF-κB and TGF-β, with potential downstream effects on mucosal inflammation and fibrotic remodelling.4 Overall, these mechanisms may contribute to improved anastomotic healing and a lower risk of early endoscopic recurrence.
- Conditions
- Chrohn's Disease
- Keywords
- anastomotic healing,, GPX4
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
• 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)
Measured: 6-12 months after IC resection.
Secondary outcomes (3)
• Association between GPX4 expression and Rutgeerts score / endoscopic recurrence
- Association between GPX4 expression and Rutgeerts score / endoscopic recurrence.
Rutgeerts score i0- no lesions (best outcome) i1- not more than 5 lesions i2 >5 lesions i3 >5 lesions i4 >5 lesions (worst outcome) is the accepted score. Is there any correlation with the levels of GPX4 (n/l/m,h) in the participants?
Measured: 6-12 months after IC resection
• Within patient change in GPX4 across pre-operative, operative and follow up tissues
- Within patient change in GPX4 across pre-operative, operative and follow up tissues
Measured: 6-12 months after IC resection
• Association between GPX4 and histological inflammation, fibrosis/stricture phenotype, or restenosis.
- Association between GPX4 and histological inflammation, fibrosis/stricture phenotype, or restenosis.
Measured: 6-12 months after IC resection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2026
- Study startNov 2026 (estimated)
- Primary completionJul 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chrohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- East Kent Hospitals University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Caroline Cowley, Study chair, East Kent Hospitals University Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07772037
- Sponsor's protocol ID
- S2026/SURG/01
- Status last verified
- Jul 2026
- First submitted
- 9 Jul 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39037448Ye 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.
PubMed 38391159Ioannidis 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.
PubMed 40489926Ma 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.
PubMed 40773274Requena 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.
PubMed 9078279Nos 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.
PubMed 18810773
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxidative Epithelial Injury After Ileocolic Resection a Retrospective Pilot Study Comparing Kono-S Versus Conventional Anastomotic Configurations Using Intestinal Epithelial GPX4 Expression.
- ClinicalTrials.gov ID
- NCT07772037
- Acronym / sponsor ID
- S2026/SURG/01
- Conditions
- Chrohn's Disease
- Keywords
- anastomotic healing,, GPX4
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- East Kent Hospitals University NHS Foundation TrustOther government
- Study start
- Nov 2026 (estimated)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 19 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Postoperative recurrence of Crohn's disease frequently occurs at or near the ileocolic anastomosis.1 Increasing evidence suggests that oxidative stress plays a central role in anastomotic healing, fibrosis and mucosal recurrence. Surgical injury triggers neutrophil recruitment and reactive oxygen species (ROS) production, which can initiate lipid peroxidation within intestinal epithelial membranes.3 Lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) activate inflammatory and fibrotic signalling pathways including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and transforming growth factor- β (TGF-β).2,4 GPX4 is a key antioxidant enzyme that detoxifies lipid peroxides and prevents ferroptosis, a regulated form of oxidative cell death.5 Reduced GPX4 activity has been described in inflammatory bowel disease and may contribute to epithelial injury and disease progression.5 Recent results have demonstrated that a reduced GPX4 expression at time of surgery predicts disease recurrence after ileocolonic resection independent of established clinical risk factors (e.g., smoking, penetrating disease, sex and age). Despite the recognised importance of oxidative stress in intestinal inflammation, its role at the surgical anastomosis in Crohn's disease has not been directly studied.
The Kono-S anastomosis is a functional end-to-end, antimesenteric configuration designed to reduce luminal distortion and faecal stasis while excluding mesenteric inflammatory influence. Early studies suggested reduced endoscopic recurrence compared with conventional anastomoses, although long-term clinical results remain mixed.6 The biological mechanisms underlying any benefit remain poorly understood.
The investigators hypothesise that the Kono-S anastomotic configuration may reduce local oxidative stress at the anastomotic site by limiting reactive oxygen species exposure and subsequent lipid peroxidation, as reflected by lower levels of markers such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) compared with conventional techniques. This more favourable redox environment may support preservation of epithelial antioxidant defence mechanisms, including maintenance of glutathione peroxidase-4 (GPX4) expression and activity, thereby reducing susceptibility of intestinal epithelial cells to ferroptosis. In turn, reduced lipid peroxidation may attenuate activation of key pro-inflammatory and pro-fibrotic signalling pathways, including MAPK, NF-κB and TGF-β, with potential downstream effects on mucosal inflammation and fibrotic remodelling.4 Overall, these mechanisms may contribute to improved anastomotic healing and a lower risk of early endoscopic recurrence.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Crohn's disease undergoing ileocolic resection, for whom suitable archived histopathology material and relevant clinical data are available.
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- • Indeterminate colitis or non-Crohn's pathology on histology.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
• Difference in epithelial GPX4 expression score between Kono-S and conventional groups at the anastomotic site 6-12 months after IC resection.
Time frame: 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)
3 secondary outcomes
• Association between GPX4 expression and Rutgeerts score / endoscopic recurrence
Time frame: 6-12 months after IC resection
• Within patient change in GPX4 across pre-operative, operative and follow up tissues
Time frame: 6-12 months after IC resection
• Association between GPX4 and histological inflammation, fibrosis/stricture phenotype, or restenosis.
Time frame: 6-12 months after IC resection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Background: PubMed 39037448Cathomas 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.
- Background: PubMed 38391159Ye 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.
- Background: PubMed 40489926Ioannidis 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.
- Background: PubMed 40773274Ma 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.
- Background: PubMed 9078279Requena 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.
- Background: PubMed 18810773Nos 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Caroline Cowley study chair
East Kent Hospitals University Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chrohn's Disease, run by East Kent Hospitals University NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe Preziosi, MD (+ 44 1843 225544., g.preziosi@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Difference in epithelial GPX4 expression score between Kono-S and conventional groups at the anastomotic site 6-12 months after IC resection. (time frame: 6-12 months after IC resection.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07772037, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.