The Effect of Inulin Supplementation on Colorectal Surgery Outcomes

Anastomotic Complication Clinical Trial

— INULINE  

Official title:

The Effect of Inulin Supplementation on Colonic Healing and Surgical Outcomes Following Colorectal Surgery

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05860322
• Other study ID #: 2023-11342
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2023
• Est. completion date: August 1, 2028

Study information

• Verified date: May 2023
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: Carole Richard, MD
• Phone: 514 890-8000
• Email: carole.richard.med[@]ssss.gouv.qc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Colorectal cancer (CRC) is the third most diagnosed cancer in Canada. The most common surgical procedure in patients with CRC is an intestinal resection followed by a reconnection to rejoin the ends of the remaining bowel. Among the postoperative complications, leaking of this intestinal connection is notably feared, affecting up to 20% of patients. These leaks are characterized by impaired intestinal healing and are associated with severe infections and even death.

Various studies have shown that gut microbiota, the bacteria that live in the digestive tract, plays an essential role in intestinal healing following surgery. These results support the possibility of enhancing intestinal healing through supplements that act as an energy source for gut bacteria. Indeed, animal studies have shown that inulin supplementation, a fiber commonly found in plants, improves intestinal healing following bowel surgery. However, no studies in humans have evaluated its effects on CRC surgery patients.

This study aims to determine feasibility of a randomized controlled trial that assesses the effects of inulin supplementation before elective colorectal surgery.

Description:

Based on preliminary data, our working hypotheses are that the gut microbiome plays a fundamental role in postoperative healing and that manipulation of preoperative microbiota using inulin will improve postoperative healing and prevent potential development of anastomotic leaks.

The pilot study aims to evaluate the feasibility of a randomized controlled trial that assesses the effects of inulin supplementation before elective colorectal surgery. The project has two main components, a clinical study, and a translational research. A randomized, multi-center, triple-blind, placebo-controlled clinical trial will be conducted to evaluate the impact of inulin supplementation on the clinical and oncological outcomes of inulin supplementation before elective colorectal oncological surgery. Mucosal, blood and fecal samples of patients with inulin supplementation will be compared with samples of patients without inulin supplementation.

The study objectives are:

1. Determine the tolerance of colorectal cancer patients to inulin supplementation before surgery.

2. Assess the effect of inulin supplementation on colonic healing and the rate of AL.

3. Determine the impact of inulin supplementation on the gut microbiota, the inflammatory markers, and the gut barrier function.

4. Assess the effect of inulin supplementation on CRC local and distant recurrence after surgery.

Identification of study participants

Patients who are about to undergo an oncological colorectal surgery will be recruited in the CHUM. Informed consent will be obtained from the patient before enrollment in the study.

Patients will be randomized to the inulin group (intervention group) or to the placebo group (control group). A stratified randomization will be conducted according to the sex (1- Male, 2-Female), the cancer location (1- Right and transverse colon, 2-Left colon and sigmoid, 3-Rectum) and the cancer grade.

Patients randomized to the intervention group will receive inulin supplementation for two weeks, preceding the surgery. Inulin will be given at a dosage of 10g/day divided in two doses. To foster compliance, the inulin will be provided in a calendar pill organizer. Patients randomized to the control group will receive a placebo for two weeks, twice a day. Placebo pills will be identical in appearance to the inulin pills. A total of 40 patients, 20 in each group, will be included in the pilot study.

Adequate colonic preparation will also be given to all the patients, including oral mechanical bowel preparation, oral antibiotics the day before surgery and intravenous antibiotics before surgical incision.

Collection of stool samples

Feces will be collected according to International Human Microbiome Standards (IHMS) guidelines (SOP 03). Two pre-operative specimens will be collected for each enrolled patient: pre-inulin/placebo supplementation and post-inulin/placebo supplementation.

Blood samples

Standard blood tests will be conducted for the participating patients. Supplementary volume will be collected during the per-operative test, before the surgery and at post-op day 3. Blood will be collected in two tubes to assess complete blood counts and to obtained serum.

Intraoperative mucosal sample

A mucosal biopsy coming from colonic anastomosis consist of a fragment from the transection line at the anastomosis. The specimen will be collected in a sterile tube and snap frozen.

Statistical Design

R, Stata and Prism will be used to perform the statistical analysis. Decision to use non-parametric tests is based on data normality (Shapiro-Wilk test) and homoscedasticity (Bartlett's test) tests. Multiple comparisons will be evaluated statistically by 1-way analysis of variance (ANOVA) or by Kruskal-Wallis test. Statistically significant differences will then be evaluated by two-tailed Student's t or Wilcoxon test. Multiple testing is corrected via False Discovery Rate estimation. For pre-supplementation and post-supplementation samples, a paired Student's t-test or paired Wilcoxon test will be used. For comparison of 2 groups, an unpaired Student's t-test or unpaired Wilcoxon test will be used.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: August 1, 2028
• Est. primary completion date: August 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a colorectal cancer and who present for elective colorectal surgery

Exclusion Criteria:

• Emergency surgery for perforation/obstruction.

• Use of antibiotics within 4 weeks prior to surgery (other than usual antibiotic prophylaxis).

• Presence of preoperative ileostomy or colostomy.

• Intestinal surgery within 4 weeks prior to colonic surgery.

• Active asthma.

• Presence of familial adenomatous polyposis.

Related Conditions & MeSH terms

• Anastomotic Complication

Intervention

Dietary Supplement:
• Inulin
Inulin is a water soluble non-digestible carbohydrate, and it is available in more than 36,000 species of plants. It is often used as dietary fiber and has obtained the "Generally recognized as safe" status (GRAS) by the Food and Drug Administration (FDA).

Other:
• Placebo
Placebo control

Locations

Country	Name	City	State
Canada	Centre hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Gastrointestinal Symptom Rating Scale (GSRS) before and after treatment.	The GSRS is a seven-point Likert-type scale with response options ranging from 1 (no discomfort at all) to 7 (very severe discomfort). It includes 15 questions that assess various gastrointestinal symptoms.	The questionnaires will be completed before treatment and after treatment (within the first week after surgery)
Primary	Change in the Digestion-associated Quality of Life Questionnaire (DQLQ) before and after treatment.	The DQLQ is a 9-item questionnaire that uses a seven-point Likert-type scale to assess the impact of gastrointestinal symptoms on quality of life. The response options range from 'never' to 'always'.	The questionnaires will be completed before treatment and after treatment (within the first week after surgery)
Secondary	Anastomotic leak rate	All patients presenting with suspicious clinical features, such as worrisome laboratory results, post-operative fever, or abnormal physical examination findings, will undergo radiological examinations to confirm an anastomotic leak.	Anastomotic leaks will be assessed clinically and, if needed, radiologically evaluated. The incidence of anastomotic leak will include cases that experience this complication during the first 12 weeks after surgery.
Secondary	White blood cell count on post-operative day 3	The white blood cell count will be monitored on post-operative day 3 to check for signs of infection or inflammation.	Blood sample will be collected on post-operative day 3.
Secondary	C-reactive protein (CRP) on post-operative day 3	The CRP will be monitored on post-operative day 3 to check for signs of infection or inflammation.	Blood sample will be collected on post-operative day 3.
Secondary	Change in fecal calprotectin levels before treatment and after treatment (on the day before surgery).	Changes in fecal calprotectin levels will be monitored to assess colonic inflammation.	Stool samples will be collected before treatment and after treatment (on the day before surgery)
Secondary	MUC2 levels in the mucosal sample	MUC2 levels will assess the amount of mucin present in the mucosa, which is important for colonic healing after surgery	The mucosal sample will be collected during surgery.