Fecal Microbiota Transplant + Dietary Fiber for Graft-versus-Host Disease

Overseen By David Fredricks

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: Bowel perforation, Inflammatory bowel disease, Celiac disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 days for FMT administration, ongoing for fiber supplementation

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies how well fecal microbiota transplant and dietary fiber supplementation work in treating patients with gut graft versus host disease. Fecal microbiota transplant entails inoculating donor stool into a recipient's gastrointestinal tract. Changing the gut microbiome by fecal microbiota transplant and fiber supplementation may help treat gut graft versus host disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation (FMT) combined with dietary fiber for graft-versus-host disease?

Research indicates that Fecal Microbiota Transplantation (FMT) has shown promise in treating intestinal graft-versus-host disease (GvHD) by restoring a healthy balance of gut bacteria. While FMT is well-documented for treating recurrent Clostridium difficile infections, its use in GvHD is still being explored, with some studies suggesting potential benefits but also highlighting the need for caution due to possible risks in immunosuppressed patients. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) generally safe for humans?

Fecal microbiota transplantation (FMT) has shown promise in treating certain conditions, but safety data is still limited, especially for long-term effects. While it is generally considered safe, there are potential risks, particularly for people with weakened immune systems, as unexpected infections may occur. ^{2 4 6 7 8}

How is the treatment Fecal Microbiota Transplantation (FMT) unique for graft-versus-host disease?

Fecal Microbiota Transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore the balance of gut bacteria, which can help manage graft-versus-host disease by improving the immune system's function. Unlike traditional treatments, FMT directly targets the gut microbiome, offering a novel approach to managing this condition. ^{2 3 9 10 11}

Research Team

David Fredricks

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for adults over 18 who had a stem cell transplant in the last 100 days and are now experiencing mild to severe gut graft versus host disease. They must not have a history of serious bowel issues or allergies to specific medications, and women must not be pregnant or breastfeeding.

Inclusion Criteria

I am 18 years old or older.

I had a stem cell transplant from a donor within the last 100 days.

I have mild to severe GI issues due to a recent transplant.

Exclusion Criteria

I have had a blockage in my intestines before.

I have had a bowel perforation in the past.

History of previous serious adverse events associated with FMT

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive fecal microbiota transplant (FMT) and dietary fiber supplementation as per randomization arm

2 days for FMT administration, ongoing for fiber supplementation

Multiple visits for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

Long-term monitoring

Participants are monitored for adverse events and quality of life

Up to 3 years

Treatment Details

Interventions

• Fecal Microbiota Transplantation
• Nutritional Supplementation

Trial Overview The study tests if fecal microbiota transplants (donor stool into the patient's gut) combined with dietary fiber can treat gut graft versus host disease after stem cell transplantation. It includes colonoscopies and surveys to monitor effects.

Participant Groups

Group I: Arm IV (Lower FMT, fiber supplementation) Experimental Treatment 5 Interventions

Patients undergo lower FMT via colonoscopy on day 0. Patients receive fiber supplementation PO while on study. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study.

Group II: Arm III (upper FMT, fiber supplementation) Experimental Treatment 4 Interventions

Patients receive upper FMT capsules PO over 2 days. Patients receive fiber supplementation PO while on study. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study.

Group III: Arm II (Lower FMT) Experimental Treatment 4 Interventions

Patients undergo lower FMT via colonoscopy on day 0. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study.

Group IV: Arm I (upper FMT) Experimental Treatment 3 Interventions

Patients receive upper FMT capsules PO over 2 days. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study.

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

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Disruptions in gut microbiota can lead to serious complications like graft-versus-host disease and infections in patients undergoing hematopoietic cell transplantation, highlighting the importance of maintaining a healthy microbiome.

Fecal microbiota transplantation (FMT) shows promise as a therapeutic intervention to restore gut health and potentially prevent adverse outcomes, but more research is needed to establish standardized protocols and best practices for its use in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward. Habibi, S., Rashidi, A.[2023]

Fecal microbiota transplantation (FMT) shows promise as a treatment for acute graft-versus-host disease (GVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT), potentially improving outcomes related to HSCT complications.

While FMT can be beneficial, it must be approached with caution due to the high risk of infections in immunosuppressed HSCT recipients, highlighting the need for careful monitoring during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease. Shouval, R., Geva, M., Nagler, A., et al.[2021]

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 transplantation (FMT) in 27 patients with gastrointestinal graft-versus-host disease (GVHD) showed significant clinical improvement, with a faster partial response compared to placebo (median 4 days vs 48 days).

FMT led to increased bacterial diversity and specific beneficial bacteria populations, such as Bifidobacterium and Bacteroides fragilis, without a higher incidence of severe adverse events, indicating it is a safe and effective treatment option for refractory GI GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety]. Goloshchapov, OV., Chukhlovin, AB., Bakin, EA., et al.[2020]

Oral fecal microbiota transplantation (FMT) capsules were successfully used to treat a 31-year-old male with corticosteroid-refractory intestinal graft-versus-host disease (GvHD), leading to symptom relief and improved gut microbiota diversity after two treatment cycles.

Despite initial success, the patient's symptoms recurred after 11 days, highlighting the need for further research to optimize treatment protocols and assess the long-term efficacy and safety of oral FMT capsules in GvHD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report. Mao, D., Jiang, Q., Sun, Y., 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 recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Fecal microbiota transplantation (FMT) has proven to be highly effective in treating recurrent Clostridium difficile infection (RCDI), especially when other treatments fail, as supported by randomized controlled trials.

While FMT shows promise for other conditions like inflammatory bowel disease, it should only be used in these cases when strong evidence of efficacy is available, and long-term safety data is still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation: current clinical efficacy and future prospects. Bowman, KA., Broussard, EK., Surawicz, CM.[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 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]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

References

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

Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease. [2021]

3. Denmark pubmed.ncbi.nlm.nih.gov

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

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

[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety]. [2020]

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

Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

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

7. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation: current clinical efficacy and future prospects. [2022]

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

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

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

Fecal Microbiota Transplantation. [2020]

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

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. [2022]