Inulin Supplementation for Anastomotic Complication

(INULINE Trial)

Overseen By Nassima Taleb

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Antibiotics

Disqualifiers: Emergency surgery, Active asthma, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude those who have used antibiotics within 4 weeks before surgery.

What data supports the effectiveness of the treatment Inulin for anastomotic complications?

Research shows that inulin, a prebiotic fiber, can improve gut health by enhancing beneficial bacteria and producing short-chain fatty acids, which help reduce inflammation and support gut barrier integrity. These effects may indirectly support healing and reduce complications in the gut, such as those that can occur after surgery. ^{1 2 3 4 5}

Is inulin safe for human consumption?

Inulin is generally considered safe and well-tolerated in humans up to 20 grams per day, with studies showing it can improve gut health and has low caloric value. ^{4 5 6 7 8}

How does inulin supplementation differ from other treatments for anastomotic complications?

Inulin supplementation is unique because it acts as a prebiotic fiber, promoting beneficial gut bacteria and producing short-chain fatty acids that can reduce inflammation and improve gut health, unlike other treatments that may not target the gut microbiota or inflammation directly. ^{1 4 5 6 9}

Research Team

Carole Richard, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for patients with colorectal cancer who are scheduled for elective bowel surgery. It's designed to see if taking inulin, a plant fiber, before their operation can help improve healing and reduce complications.

Inclusion Criteria

I have colorectal cancer and am scheduled for elective surgery.

Exclusion Criteria

I have a stoma from previous surgery.

I haven't taken antibiotics in the last 4 weeks, except for prevention.

I have been diagnosed with familial adenomatous polyposis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive inulin or placebo supplementation for 14 days before surgery

2 weeks

Daily self-administration

Surgery

Participants undergo elective colorectal surgery

1 day

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for post-operative complications and healing, including blood tests and mucosal sample collection

3 days

In-patient monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of anastomotic leaks and quality of life

12 weeks

Regular follow-up visits

Treatment Details

Interventions

• Inulin
• Placebo

Trial Overview The study is testing the effects of inulin supplementation versus a placebo on the outcomes of colorectal surgery. Participants will be randomly assigned to receive either inulin or a placebo before their surgery.

Participant Groups

Group I: Inulin group Experimental Treatment 1 Intervention

Patients randomized to the intervention group will receive inulin supplementation for 14 days, preceding the surgery. Inulin will be given at a dosage of 10g/day divided in two doses.

Group II: Control group Placebo Group 1 Intervention

Patients randomized to the control group will receive a placebo for 14 days, two times a day.

Inulin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Inulin for:

• Dietary supplement
• Prebiotic

Approved in United States as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Canada as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Japan as Inulin for:

• Dietary supplement
• Prebiotic

Approved in China as Inulin for:

• Dietary supplement
• Prebiotic

Approved in Switzerland as Inulin for:

• Dietary supplement
• Prebiotic

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

Inulin-rich meat products, such as chorizo sausages and cooked ham, significantly reduced colon polyp formation by 49% in an animal model, indicating their potential as preventive foods against colorectal cancer.

The functional meat products not only increased beneficial short-chain fatty acids like propionate and butyrate but also altered gut microbiota composition, enhancing beneficial bacteria while reducing pro-inflammatory populations, suggesting a multifaceted approach to cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models. Fernández, J., Ledesma, E., Monte, J., et al.[2023]

Fermentation of various dietary fibers, particularly oat β-glucan, significantly enhances gut barrier integrity and mucus production, suggesting these fibers can improve gut health.

In models of compromised gut barriers, oat β-glucan and maltodextrin fermentation products were particularly effective in restoring gut integrity, highlighting their potential as therapeutic agents for gut-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro. Pham, VT., Seifert, N., Richard, N., et al.[2020]

In a 3-month randomized, placebo-controlled trial involving 24 obese patients, the intake of inulin-type fructans (ITF) significantly increased levels of beneficial gut bacteria, specifically Bifidobacterium, and reduced fecal calprotectin, a marker of gut inflammation.

The study suggests that ITF may help improve gut health in obese individuals by decreasing inflammation and potentially influencing gut microbiota-derived metabolites, although it did not significantly change short-chain fatty acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. Neyrinck, AM., Rodriguez, J., Zhang, Z., et al.[2022]

Fermentation supernatant fractions of inulin significantly increased short-chain fatty acids (SCFA) and decreased harmful bile acids, showing potential protective effects against colorectal cancer.

In human colon cell lines, particularly in early-stage cancer cells (LT97), the fermentation supernatant induced apoptosis and inhibited cell growth, suggesting that prebiotic fibers like inulin could play a role in cancer chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Munjal, U., Glei, M., Pool-Zobel, BL., et al.[2022]

Inulin fructans, derived from chicory root, are safe and well-tolerated dietary fibers that can be consumed up to 20 g per day, providing various health benefits.

They have direct effects on gut health, such as improving bowel function and promoting beneficial gut bacteria, as well as indirect effects on blood lipids and the immune system, suggesting potential for further research in energy balance and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of Inulin Fructans in the Human Diet. Schaafsma, G., Slavin, JL.[2021]

In a study using fecal cultures from healthy and morbidly obese adults, different prebiotics were tested, revealing that 1-kestose had the most significant impact on gut microbiota composition and metabolic activity.

Prebiotic modulation led to increased Bacteroides and Faecalibacterium in obese individuals, while normal-weight individuals showed higher levels of Bifidobacterium and Faecalibacterium, highlighting the need for tailored prebiotic treatments based on individual microbiota profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Prebiotics on the Modulation of Gut Microbiota Composition and Function in Morbid Obese and Normal-Weight Subjects. Nogacka, AM., Salazar, N., Arboleya, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of fermentation products of prebiotic fibres on gut barrier and immune functions in vitro. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Inulin and oligofructose: impact on intestinal diseases and disorders. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Prebiotic dietary fibre intervention improves fecal markers related to inflammation in obese patients: results from the Food4Gut randomized placebo-controlled trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Significance of Inulin Fructans in the Human Diet. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Prebiotics on the Modulation of Gut Microbiota Composition and Function in Morbid Obese and Normal-Weight Subjects. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Xylo-oligosaccharides and inulin affect genotoxicity and bacterial populations differently in a human colonic simulator challenged with soy protein. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. [2019]