Fecal Microbiota Transplantation for Colitis

Overseen By Suchitra K Hourigan, M.D.

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: Acute GI infection, C difficile, 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: 10

Duration: 3-5 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether placing healthy bacteria from donor stool into the intestines, known as fecal microbiota transplantation (FMT), can reduce inflammation in individuals with chronic granulomatous disease (CGD) who also have colitis. CGD weakens the body's defense against germs and can damage the colon, leading to inflammation. The trial includes a 3-5 day hospital stay for the FMT procedure, followed by several follow-up visits. It is suitable for individuals aged 10-60 with CGD and colitis, particularly if current treatments are ineffective or cause side effects. Participants will be closely monitored over 6-7 months to assess the treatment's impact on their symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that there be no planned changes in your systemic antibiotic regimen for CGD or escalation in CGD-IBD treatment for 1 month before the FMT. If you are taking monoclonal antibodies for CGD-IBD, the dose must be stable for 12 weeks with no planned increase.

What prior data suggests that fecal microbiota transplantation is safe for colitis?

Research has shown that fecal microbiota transplantation (FMT) is safe and effective for treating certain conditions, such as Clostridioides difficile infection (CDI), in children and young adults. Patients typically handle the procedure well, with few side effects.

Studies using the OpenBiome FMT product have shown similar safety results, with patients experiencing minimal side effects. FMT introduces healthy bacteria from donor stool into the gut to restore balance and reduce inflammation. For individuals with chronic granulomatous disease (CGD) and colitis, this approach might provide relief when other treatments have failed.

In summary, while all medical treatments carry some risks, previous studies have generally found FMT to be well-tolerated. This suggests it could be a promising option for those with CGD-related colitis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about fecal microbiota transplantation (FMT) for colitis because it offers a novel approach by using healthy donor stool to restore the gut microbiome. Unlike standard treatments for colitis, such as anti-inflammatory drugs and immunosuppressants, FMT aims to directly rebalance gut bacteria, potentially addressing the root cause of inflammation. Delivered via colonoscopy, this method allows for a targeted introduction of beneficial microbes, which might lead to improved outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that fecal microbiota transplantation might be an effective treatment for colitis?

Research has shown that fecal microbiota transplantation (FMT) could help treat conditions like inflammatory bowel disease (IBD) by introducing healthy bacteria to the gut. Studies have found FMT effective and safe for treating Clostridioides difficile infection (CDI) in children and young adults. This trial will explore FMT as a treatment for colitis associated with chronic granulomatous disease (CGD). The goal is to restore balance and reduce inflammation in the intestines by introducing beneficial bacteria from donor stool. Early findings in similar conditions support FMT as a potential treatment option. ^{1 2 3 4 5}

Who Is on the Research Team?

Suchitra K Hourigan, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for people aged 10-60 with Chronic Granulomatous Disease (CGD) and colitis who haven't responded well to other treatments. They must have a specific level of inflammation marker in their stool, no recent changes in antibiotics or escalation in CGD treatment, and if they can get pregnant, agree to use effective contraception.

Inclusion Criteria

HBI score >=5 (to be evaluated on Day 1)

I've been on a stable dose of monoclonal antibodies for my condition for 12 weeks.

I am over 18 and can consent, or if under 18, my guardian can.

Exclusion Criteria

Any condition that, in the opinion of the investigator, contraindicates participation in this study

Pregnant or breastfeeding

I have had complications from inflammatory bowel disease, like fistulas or abscesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (telehealth)

Treatment

Participants receive fecal microbiota transplantation (FMT) delivered by colonoscopy

3-5 days

Inpatient stay at NIH hospital

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

9 visits (telehealth), up to 2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• OpenBiome FMT product FMP250

Trial Overview The trial tests whether transplanting good bacteria from donor stool into the intestines (Fecal Microbiota Transplantation - FMT) can reduce colon inflammation in CGD patients. Participants will undergo various tests including a colonoscopy to deliver the FMT material and follow-up telehealth visits over 6 months.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 1 Intervention

As this is a single arm study, this arm includes all participants. Participants will receive fecal microbiota transplantation (FMT) delivered by colonoscopy as a treatment for chronic granulomatous disease (CGD)-associated colitis (AC).

OpenBiome FMT product FMP250 is already approved in United States, European Union for the following indications:

Approved in United States as OpenBiome FMT product FMP250 for:

• Clostridioides difficile infection (CDI)
• Chronic Granulomatous Disease-Associated Colitis (CGD-AC)

Approved in European Union as OpenBiome FMT product FMP250 for:

• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a trial involving 35 patients with active ulcerative colitis, oral lyophilised faecal microbiota transplantation (FMT) led to a significant remission rate, with 53% of patients achieving corticosteroid-free clinical remission compared to 15% in the placebo group.

Continuing FMT after initial treatment resulted in 100% of patients maintaining remission at week 56, suggesting that oral FMT could be a promising long-term treatment option for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. Haifer, C., Paramsothy, S., Kaakoush, NO., et al.[2022]

In a survey of 262 ulcerative colitis patients, 56.1% expressed willingness to undergo fecal microbiota transplantation (FMT) as a treatment option, motivated primarily by the effectiveness of the procedure and the failure of other therapies.

Concerns about FMT included the potential transmission of infectious agents and contamination of the stool graft, highlighting the need for safe implementation practices in this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. Roggenbrod, S., Schuler, C., Haller, B., et al.[2022]

In a pilot study of 20 patients with active ulcerative colitis, 35% achieved a clinical response and 15% reached remission after a single fecal microbiota transplantation (FMT) using a high-diversity, 2-donor fecal microbiota preparation, indicating its potential efficacy.

The study found that FMT significantly increased the diversity of the gut microbiome in patients, and the composition of the donor microbiota was linked to clinical outcomes, suggesting that donor selection may play a crucial role in treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis. Jacob, V., Crawford, C., Cohen-Mekelburg, S., et al.[2022]

Patients who received fecal microbiota transplantation (FMT) for ulcerative colitis reported high satisfaction and preferred FMT over conventional medications, indicating its potential as an effective treatment option.

The study highlighted the importance of patient education, as both FMT and non-FMT patients had concerns about cleanliness and a lack of understanding about the procedure, which could affect acceptance of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis: A Qualitative Assessment of Patient Perceptions and Experiences. Chauhan, U., Popov, J., Farbod, Y., et al.[2022]

The rat model is more effective than the mouse model for studying human microbiota engraftment, as it shows greater similarity to human microbial communities and captures more human microbial species after fecal microbiota transplantation (FMT).

A single human stool transfer (HST) significantly improved colitis symptoms in rats by restoring microbial diversity and reducing inflammation, with even better results when inflammation was controlled prior to the transfer, suggesting a potential combined therapy approach with anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis. Lleal, M., Sarrabayrouse, G., Willamil, J., et al.[2020]

Fecal microbiota transplantation (FMT) showed effectiveness in treating active ulcerative colitis (UC) in a small study of 7 patients, with all participants experiencing improvements in their Mayo scores after the procedure.

While some patients experienced mild and transient side effects like fever and diarrhea, no severe adverse reactions were reported, suggesting that FMT is a relatively safe option for managing active UC, although further research is needed to assess long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation]. Ren, R., Sun, G., Yang, Y., 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]

The study demonstrated that daily oral administration of frozen encapsulated fecal microbiota transplantation (cFMT) is safe and well-tolerated in patients with mild to moderate ulcerative colitis (UC), with no treatment-related adverse events reported.

Two out of six subjects receiving cFMT achieved clinical remission, suggesting that cFMT may help maintain beneficial changes in gut microbiota and improve clinical outcomes, although further research is needed to confirm these findings and address home storage issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. Crothers, JW., Chu, ND., Nguyen, LTT., et al.[2022]

In a study of 30 patients with ulcerative colitis who did not respond to standard treatments, 70% showed a clinical response to fecal microbial transplantation (FMT) after 12 weeks, with 43.3% achieving both clinical and endoscopic remission.

FMT was found to be a safe alternative to immunosuppressive therapies, with only mild adverse events reported in 23.3% of patients, suggesting it could be a promising option for those with refractory ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Uygun, A., Ozturk, K., Demirci, H., et al.[2018]

Fecal microbiota transplantation (FMT) significantly improved gastrointestinal symptoms and reduced depression and anxiety in 30 patients with refractory irritable bowel syndrome (IBS), with sustained benefits observed 3-6 months post-treatment.

The safety profile of FMT was favorable, with only a 6.7% adverse event rate, and responders showed increased gut microbiota diversity and specific bacterial changes, indicating a potential mechanism for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota. Huang, HL., Chen, HT., Luo, QL., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05333471

Study Details | NCT05333471 | Fecal Microbiota ... This is a prospective, single-site, single-arm, open-label pilot trial to evaluate the use of fecal microbiota transplantation (FMT) delivered by colonoscopy as ...

2. openbiome.org openbiome.org/publications/

Publications – The OpenBiome Foundation Findings from a large multi-center retrospective cohort, found FMT is effective and safe for the treatment of CDI in children and young adults.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10133790/

Fecal transplantation for treatment of inflammatory bowel ... To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no ...

4. openbiome.org openbiome.org/

The OpenBiome Foundation OpenBiome Foundation's mission is to expand patient access to microbiome therapies and drive scientific discoveries that shape the future of health.

5. withpower.com withpower.com/trial/phase-2-colitis-4-2022-194da

Fecal Microbiota Transplantation for Colitis This trial is testing if placing healthy bacteria from donor stool into the intestines of people with CGD and colitis can reduce inflammation.