Characterising the Natural History of Mucosal Metabolism During Colorectal Anastomotic Healing

This pilot study aims to investigate anastomotic healing and its underlying mechanisms at a mucosal level. It is a first-in-human study which will demonstrate the safety of post-operative endoscopic assessment of a colorectal anastomosis and provide preliminary data in order to power future interventional studies.

100 patients undergoing elective left colonic or rectal resection with a primary anastomosis will be recruited pre-operatively throughout the study period. This study will not affect or delay the intended treatment for study participants.

Patients will undergo serial endoscopic examination of the anastomosis post-operatively. Blood, urine, stool, and mucosal biopsies will be serially collected.

A subgroup of 20 patients with a defunctioning ileostomy will be recruited to an interventional arm. This interventional arm will demonstrate the safety of re-introducing ileostomy effluent into the downstream (distal) limb of an ileostomy. The preliminary data will enable exploration of the association between microbiome and post-operative function and enable adequate powering of future interventional studies.

Study Overview

• Status: Recruiting
• Conditions: Healing of Colorectal Anastomoses
• Intervention / Treatment: Other: Distal limb reintroduction of ileostomy effluent

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: James Kinross, PhD FRCS; Phone Number: 020 3312 2124; Email: j.kinross@imperial.ac.uk
• Study Contact Backup: Name: James Lewis, MRCS; Phone Number: 020 3312 2124; Email: james.lewis1@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: James Kinross, PhD FRCS; Phone Number: 020 3312 2124; Email: j.kinross@imperial.ac.uk
    • Contact: James Lewis, MBBS; Phone Number: 020 3312 2124; Email: james.lewis1@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients undergoing elective left sided colonic or rectal resections with primary anastomosis with or without diverting ileostomy.

Exclusion Criteria:

• Inability to communicate in English
• People who lack capacity to consent
• Emergency colorectal resection whilst awaiting elective surgery
• Age <18
• Permanent stoma formation
• People on long term immunosuppressive medication
• People on long term renal replacement therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational cohort; 100 patients undergoing elective left colonic or rectal resection with a primary anastomosis will be recruited pre-operatively throughout the study period. This study will not affect or delay the intended treatment for study participants. Patients will undergo serial endoscopic examination of the anastomosis post-operatively. Blood, urine, stool, and mucosal biopsies will be serially collected.
Experimental: Distal limb feeding cohort; This interventional arm will demonstrate the safety of re-introducing ileostomy effluent into the downstream (distal) limb of an ileostomy. The preliminary data will enable exploration of the association between microbiome and post-operative function and enable adequate powering of future interventional studies. A subgroup of 20 patients undergoing a resection with a covering ileostomy will be recruited to the intervention arm. Complete healing of the colorectal anastomosis will first be confirmed by water-soluble contrast enema 8 weeks post-operatively (this is standard practice). Patients will be taught how to inject the output from the proximal ileostomy limb into the distal limb (this connects to the colon and thus the colorectal anastomosis) daily until the ileostomy closure date.	Other: Distal limb reintroduction of ileostomy effluent; Patients will undergo water soluble contrast enema to confirm anastomotic healing 8 weeks post operatively as per standard practice at Imperial. Patients will be educated in how to reintroduce ileostomy output to the distal (downstream) loop of their ileostomy. They will be asked to reintroduce 50ml of ileostomy output using a conventional long-tipped bladder syringe daily until surgery to close the stoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anastomotic healing	Healing of the colorectal anastomosis when assessed endoscopically - with no visible defects in the anastomosis.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure of anastomotic healing	Anastomotic leak detected either by radiological imaging (CT scanning) or a direct return to theatre	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in microbial diversity	Changes in microbial abundance and diversity at the anastomosis. The nature of any change is as yet not investigated and unpredictable - this is an observational outcome measure.	1 year

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IRAS 246354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No