Microbiota Transplant for Colon Resection

Overseen By Kathryn Vera

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Inflammatory bowel disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 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?

This is a single-center, open-label study for safety and feasibility of IMT in patients undergoing colonic surgery. After consent, individuals of the ages of 18-75 with a history of diverticulitis or sigmoid colon cancer will be enrolled to have a feeding tube placed at the time of surgery and receive IMT solution on postoperative day 2-3 (at least 48 hours following IV antibiotics) with the subsequent removal of the feeding tube. Prior to administration of IMT, recipients will be screened for inclusion/exclusion criteria, interviewed for medical history and medications, and consented. Additionally, prior to undergoing IMT, baseline blood and fecal samples will be collected. The use of a nasogastric feeding tube has specifically been chosen over colonoscopic introduction of the IMT. This is because colonoscopy introduces increased intraluminal carbon dioxide and pressure as well as mechanical stress on the colon in the setting of a newly created bowel anastomosis, which may contribute to the potential risk of anastomotic disruption. The nasogastric feeding tube will be placed while the patient is under anesthesia under direct visualization to minimize any risk of bowel perforation, albeit very low. The study will specifically utilize a 10F 43" Corpak feeding tube (Halyard Health, Alpharetta, GA). Patients will be monitored while in-patient in person. Following discharge, they will undergo follow-up either by phone, video or in-person visit, or via online survey of symptoms and chronic medical conditions potentially related to IMT, beginning on the day following discharge through post-operative day 14, and then monthly up to 6 months post- IMT to screen for SAEs and AEs. Screening for SAEs and AEs will be done using a symptom questionnaire as well as by asking patients during our interview. Fecal samples will be collected from participants on months one, three and six post-IMT to assess for changes in recipient microbiome (engraftment kinetics).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressants or receiving cancer treatments, you would not be eligible to participate.

What data supports the effectiveness of the treatment Intestinal Microbiota Transplantation for colon resection?

The treatment, known as fecal microbiota transplantation (FMT), is well-documented to be effective for recurrent Clostridium difficile infections, but there is not enough evidence yet to recommend it for other gastrointestinal diseases, including those related to colon resection. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to delivery methods. However, serious adverse events have been associated with FMT products from stool banks that do not screen for multi-drug resistant organisms, so strict donor screening is important. ^{6 7 8 9 10}

How is the treatment Intestinal Microbiota Transplantation unique for colon resection?

Intestinal Microbiota Transplantation (also known as Fecal Microbiota Transplantation) is unique because it involves transferring stool from a healthy donor to restore the natural balance of bacteria in the gut, which is different from traditional treatments that might rely on medications or surgery. This approach is particularly novel as it aims to directly modify the gut microbiome to improve health outcomes. ^{1 4 5 11 12}

Research Team

Cyrus Jahansouz, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults aged 18-75 who have had diverticulitis and are undergoing colon resection surgery. Participants will receive either an intestinal microbiota transplant (IMT) or a saline solution through a feeding tube after surgery. They must meet certain health criteria, not be allergic to the materials used, and agree to follow-up assessments.

Inclusion Criteria

I am willing and able to follow all study requirements and stay in touch as needed.

Able/willing to provide informed consent

I am between 18 and 75 years old.

Exclusion Criteria

I have had a solid organ or bone marrow transplant.

I have an ileostomy or colostomy.

I have been diagnosed with celiac disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery and IMT Administration

Participants undergo colon resection surgery and receive IMT solution via nasogastric feeding tube on postoperative day 2-3

1 week

In-patient monitoring

Immediate Postoperative Follow-up

Participants are monitored for safety and effectiveness, including adverse events, from discharge through post-operative day 14

2 weeks

Follow-up by phone, video, in-person, or online survey

Long-term Follow-up

Participants are monitored monthly up to 6 months post-IMT for safety and changes in microbiome

6 months

Monthly follow-up by phone, video, in-person, or online survey

Treatment Details

Interventions

• Intestinal Microbiota Transplantation

Trial Overview The study tests the safety of delivering IMT via a nasogastric feeding tube compared to a saline solution in patients post-colon surgery. It aims to see if this method is feasible without causing harm like bowel perforation or disrupting the surgical site.

Participant Groups

Group I: IMT group Experimental Treatment 1 Intervention

individuals of the ages of 18-75 with a history of diverticulitis or sigmoid colon cancer will be enrolled to have a feeding tube placed at the time of surgery and receive either IMT solution

Intestinal Microbiota Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Fecal microbiota transplantation (FMT) is primarily effective for treating recurrent Clostridium difficile infections by restoring a healthy microbiome in the colon.

Currently, there is not enough evidence to support the use of FMT for other gastrointestinal or nongastrointestinal diseases, although research is ongoing in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. Vindigni, SM., Surawicz, CM.[2020]

Faecal microbiota transplantation (FMT) has proven effective for treating recurrent Clostridium difficile infections, with established protocols and donor stool banks in Denmark.

However, FMT is not recommended for routine use in treating inflammatory bowel disease or irritable bowel syndrome due to insufficient clinical trial data supporting its efficacy for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. Rode, AA., Chehri, M., Petersen, AM., et al.[2019]

Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infections, highlighting its established role in restoring gut health.

There is growing interest in exploring FMT's potential benefits for other gastrointestinal diseases linked to dysbiosis, suggesting it may have broader therapeutic applications beyond just C. difficile infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases. Núñez F, P., Quera, R., Bay, C., et al.[2022]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

Fecal microbiota transplantation (FMT) is an effective method for restoring healthy gut flora in patients suffering from Clostridium difficile infection (CDI).

There is a need for further research to understand how FMT can be safely and effectively used in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in patients with cancer undergoing treatment. Blackburn, LM., Bales, A., Caldwell, M., et al.[2020]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

Fecal microbiota transplantation (FMT) has a reported adverse event (AE) rate of 39.3%, primarily involving mild and self-limiting issues like abdominal pain and diarrhea, based on a meta-analysis of 9 high-quality studies involving 756 FMTs.

Serious adverse events (SAE) were relatively rare at 5.3%, with the most common being Clostridium difficile infection, indicating that while FMT is generally safe, monitoring and standardized reporting are essential for understanding its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Michailidis, L., Currier, AC., Le, M., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

In a follow-up study of 77 IBS patients who previously responded to fecal microbiota transplantation (FMT), 86.5% of those receiving 30-g and 87.5% of those receiving 60-g FMT maintained their positive response after 1 year.

Improvements in abdominal symptoms and quality of life continued to increase over the year, alongside significant changes in the fecal bacterial profile and levels of short-chain fatty acids, indicating the long-term efficacy and safety of FMT for IBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. El-Salhy, M., Kristoffersen, AB., Valeur, J., et al.[2022]

Fecal microbiota transplantation (FMT) has proven to be highly effective in treating recurrent and refractory Clostridioides difficile infections (CDI), leading to a surge in research on gut microbiota therapies.

The future of microbiome-based treatments is expected to focus on developing oral formulations with known ingredients, clear mechanisms of action, and strong safety profiles, expanding the potential applications of FMT beyond CDI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. Kumar, V., Fischer, M.[2020]

Fecal microbiota transplantation (FMT) effectively normalizes the gut microbiota in patients with recurrent Clostridium difficile infection, showing significant changes within just one day after the procedure.

While the microbiota composition initially resembles that of the donor, it diverges over time, indicating that the gut microbiome is dynamic and requires ongoing monitoring to evaluate the long-term success of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Weingarden, A., González, A., Vázquez-Baeza, Y., et al.[2018]

References

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

Fecal Microbiota Transplantation. [2020]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Faecal microbiota transplantation for the treatment of bowel disease]. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases. [2022]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. [2022]

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

Fecal microbiota transplantation in patients with cancer undergoing treatment. [2020]

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

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

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

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

10. England pubmed.ncbi.nlm.nih.gov

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. [2018]