Comparing Surgical Approaches for Crohn's Disease Recurrence

January 26, 2024 updated by: Sixth Affiliated Hospital, Sun Yat-sen University

Mesentery Guided Resection Versus Traditional Ileocolic Bowel Resection in Reducing Early Endoscopic Recurrence Rate After Ileocolic Crohn 's Disease Surgery:a Prospective, Multicenter, Randomized Controlled Clinical Trial

Despite significant advancements in the treatment of Crohn's disease (CD), approximately 50% of patients undergo surgical intervention within ten years of diagnosis. Furthermore, more than 70% of these patients experience endoscopic recurrence within one year after surgery. This subset of patients often faces a poorer long-term prognosis and requires long-term intensified medical therapy. Therefore, reducing early postoperative endoscopic recurrence has remained a crucial focus in CD research.

From a surgical perspective, there have been limited breakthroughs in improving surgical techniques to reduce the postoperative endoscopic recurrence rate in CD. Recent research indicates that microscopic inflammation at the cut edge of the CD bowel segment is a significant risk factor for postoperative endoscopic recurrence. Mesenteric wrapping is a unique clinical pathological feature of CD. Our retrospective data suggest a clear linear correlation between the degree of mesenteric wrapping and microscopic inflammation in the corresponding bowel segment. Surgical margins determined by mesenteric guidance significantly reduce the postoperative endoscopic recurrence rate and clinical relapse rate compared to the traditional 2 cm margin. However, there is currently no prospective study comparing the efficacy of these two surgical approaches.To address this, investigators plan to conduct a multicenter randomized controlled trial. This trial will focus on patients with ileocolonic CD who have undergone primary anastomosis without residual disease. investigators aim to compare the postoperative endoscopic recurrence rates between mesenteric-guided margins and the traditional 2 cm margins. Our goal is to determine whether mesenteric-guided margins can reduce the postoperative endoscopic recurrence rate and to conduct relevant mechanistic research. Ultimately, this research may lead to the development of a novel surgical approach for CD based on the findings of this study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Current Status of the Study Current Status of the Study While treatment methods for Crohn's disease (CD) have made significant advancements, there is still a 50% requirement for surgical intervention within 10 years of diagnosis (1). The most common surgical procedures include ileocecal or terminal ileal resection. However, post-surgery, the risk of recurrence remains high, with 35% to 85% of patients experiencing endoscopic recurrence within one year (2, 4), and clinical recurrence occurring in 10% to 38% of patients within one year, leading to a need for reoperation in 30% of patients within five years (2, 3). Several studies have demonstrated that early endoscopic recurrence at six months post-surgery can effectively predict long-term treatment outcomes and guide subsequent medication choices (5).

Therefore, reducing early endoscopic anastomotic recurrence post-surgery has been a focus of CD research. The quality of surgical procedures significantly impacts this outcome. Previous research has identified risk factors for post-surgical recurrence, including smoking history, previous bowel resections, penetrating disease, extensive involvement, and concomitant perianal disease (6-8). However, these are non-modifiable patient-related factors. Within the scope of what physicians can control, proactive preventive treatment approaches adopted by gastroenterologists have been shown to reduce endoscopic recurrence rates to some extent. Nevertheless, the role and responsibilities of surgeons in this regard have not been clearly defined, and thus, there is a lack of standardized surgical strategies to reduce early endoscopic recurrence.（11） Intestinal mesentery abnormal proliferation and wrapping around the mesenteric margin is a characteristic pathological feature of Crohn's disease (CD). Recent studies have shown that mesenteric fat plays a crucial role in the development of CD (13, 14). The applicant's research team has also discovered the presence of bacteria displaced from the intestines within the mesentery, which can stimulate the proliferation of fat cells (15). Our preliminary retrospective data (pending submission) also suggests that if the mesenteric-guided margin, corresponding to the border of mesenteric abnormality, is used as the resection margin, even though an average of 10cm more intestine is removed, the postoperative endoscopic recurrence rate and clinical recurrence rate are significantly better than those of patients with the traditional limited 2cm margin (as described in the research foundation). However, there is currently no prospective randomized controlled study comparing these two margin strategies. Therefore, investigators plan to conduct a prospective multicenter randomized controlled study for patients with ileocolonic CD who undergo primary anastomosis without residual disease, comparing the postoperative endoscopic recurrence rates between mesenteric-guided margins and traditional 2cm margins, and conducting related mechanistic research to establish a high-level evidence for surgical margins that can reduce postoperative endoscopic recurrence in CD.

The significance of this research lies in addressing the issue of high endoscopic recurrence rates following surgery for Crohn's disease (CD), for which there is currently no established surgical solution. This study employs an innovative approach by using the mesenteric fat boundary as guidance for surgical resection margins, making it a novel contribution to both national and international research.

Building upon prior preliminary research, our research team aims to determine, through a prospective multicenter study, whether the use of mesentery-guided resection margins can reduce the endoscopic recurrence rate, while also exploring potential underlying mechanisms. The successful implementation of this project can provide high-level evidence for the correct selection of surgical margins in CD, fostering the development of personalized and precision surgical approaches in the treatment of CD in China, offering substantial clinical application and practical guidance.The ultimate goal of this study is to improve the long-term prognosis of CD patients and enhance their postoperative .

Study Type

Interventional

Enrollment (Estimated)

114

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Patients with a clear diagnosis of CD who meet the surgical indications and will undergo one-stage ileocecal resection.
  2. Ileocecal CD with localized lesions involving the terminal ileum and cecum, with a total lesion length of <60 cm.
  3. Patients or their legal guardians who can understand and are willing to participate in this study, provide written informed consent, and have the ability to comply with the protocol.

Exclusion criteria:

  1. Patients with a history of previous ileocecal resection.
  2. Patients with primary lesions in other locations (e.g., proximal small bowel) that require surgical resection of inflamed intestinal segments other than the ileocecal region (excluding cases with affected other segments of the bowel).
  3. Patients with a lesion length in the terminal ileum ≥60 cm.
  4. Patients who only require ileal resection (excluding the ileocecal area), as this surgical procedure preserves the most distal ileum and the ileocecal valve.
  5. Patients who require ileostomy formation.
  6. Patients who have suffered from serious illnesses within the six months before surgery, such as myocardial infarction, active angina pectoris, congestive heart failure, or other diseases believed by the investigator to pose a risk to the patient's safety.
  7. Patients with a history of malignant tumors, including melanoma (excluding localized skin cancer).
  8. Patients clinically diagnosed with autoimmune diseases other than CD or with evidence of other autoimmune diseases.
  9. Pregnant or lactating patients.
  10. Patients who cannot be tracked at various study time points for the primary outcome measure.

Withdrawal criteria:

  1. Subjects lost to follow-up or voluntarily requesting withdrawal.
  2. The occurrence of anastomotic fistula after surgery that affects subsequent endoscopic evaluation.
  3. Subjects considered unsuitable for further participation in the study by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: mesentery-guided resection margin group
The research team positions the proximal margin of the anastomosis in a way that the mesentery reaches the point of being palpable and where the fat appears entirely normal under direct visual observation, in contrast to the mesentery near the proximal and distal ends of the anastomosis.
Procedure: mesentery-guided resection margin
The research team positions the proximal margin of the anastomosis in a way that the mesentery reaches the point of being palpable and where the fat appears entirely normal under direct visual observation, in contrast to the mesentery near the proximal and distal ends of the anastomosis.
No Intervention: traditional resection margin group
The proximal margin is defined as being 2 cm from the point where visible mucosal lesions are present. Macroscopic lesions are defined as visible pathologies such as intestinal narrowing, thickening of the intestinal wall, or mucosal ulcers. In both groups, the distal margin is located at the hepatic flexure of the ascending colon, where both the mesentery and the intestinal wall are macroscopically normal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Modified Rutgeerts Score during colonoscopy
Time Frame: At 6 months after surgery.
A Rutgeerts score > i2b is defined as endoscopic recurrence. Calculate the endoscopic recurrence rates in both groups and compare them using a chi-square test to determine if there is a significant difference between the two groups.
At 6 months after surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To calculate the endoscopic recurrence rate for both groups within 1 year
Time Frame: At 1 year after surgery.
Endoscopic Recurrence Rate = (Number of Patients with Endoscopic Recurrence / Total Number of Patients in the Group) * 100. Compare the recurrence rates between the two groups and determine if there is a significant difference, you can perform a chi-squared test.
At 1 year after surgery.
Compare the clinical recurrence rates between the two groups
Time Frame: At 1 year after surgery.
After the surgery, patients are required to undergo Crohn's Disease Activity Index (CDAI) scoring every 6 months. Patients with a CDAI score ≥150 are defined as experiencing clinical relapse. Clinical relapse rates for both groups are calculated (number of patients with clinical relapse in each group divided by the total number of patients in each group). A chi-squared test is then employed to compare if there are any differences in relapse rates between the two groups.
At 1 year after surgery.
Calculate the rate of requiring a second surgery for both groups
Time Frame: At 3 years after surgery.
Second surgery rate (number of individuals requiring a second surgery in each group divided by the total number in each group), and use the chi-squared test to compare whether there is a difference in the recurrence rates between the two groups.
At 3 years after surgery.
Compare the postoperative margin pathology between the two surgical methods.
Time Frame: At 7 days after surgery
In both the mesentery-guided margin and traditional limited resection specimens, within the range of 5-10 cm from the near margin (or up to the location of the diseased bowel segment), full-thickness pathological slides were taken every 1-2 cm (including the parts adjacent to the bowel mesentery) to assess if there is submucosal inflammation in the locations close to the macroscopic lesion and mesenteric abnormality.
At 7 days after surgery
Comparison of the length of bowel resection and intestinal function between the two surgical methods
Time Frame: At 7 days after surgery
Calculate the average length of bowel resection in both groups and use a t-test to compare if there is a significant difference in resection length between the two groups.
At 7 days after surgery
Comparison of the intestinal function of paticipants between the two surgical methods
Time Frame: At 3 years after surgery.
Evaluate postoperative bowel function using the GSRS scale, and require participants to complete the GSRS assessment every 6 months after surgery. Calculate the average GSRS scores in both groups and compare if there is a significant difference in GSRS scores between the two groups
At 3 years after surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Collaborators

First Affiliated Hospital, Sun Yat-Sen University

Investigators

  • Principal Investigator: Jia Ke, M.D., Sixth Affiliated Hospital, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

November 8, 2023

First Submitted That Met QC Criteria

January 26, 2024

First Posted (Actual)

February 5, 2024

Study Record Updates

Last Update Posted (Actual)

February 5, 2024

Last Update Submitted That Met QC Criteria

January 26, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022ZSLYEC-159

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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