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 is testing if placing healthy bacteria from donor stool into the intestines of people with CGD and colitis can reduce inflammation. The target group is patients aged 10-60 who haven't responded to other treatments. The goal is to restore a healthy balance of gut bacteria to reduce inflammation. This method has shown promise in treating inflammatory bowel diseases like ulcerative colitis by restoring a healthy gut balance.

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.

Is fecal microbiota transplantation (FMT) safe for humans?

FMT has been used to treat various gastrointestinal conditions, and while it shows promise, the safety data is still limited. Short-term side effects can occur, and long-term safety is not well understood yet, but ongoing research aims to improve safety and tolerability. ^{1 2 3 4 5}

How is fecal microbiota transplantation different from other treatments for colitis?

Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore healthy gut bacteria, unlike traditional medications that target symptoms or inflammation directly. This treatment can be administered through colonoscopy, enemas, or potentially oral capsules, and aims to increase microbial diversity in the gut, which may help induce remission in ulcerative colitis. ^{1 4 6 7 8}

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation for Colitis?

Research shows that fecal microbiota transplantation (FMT) can be effective for treating ulcerative colitis, a type of inflammatory bowel disease. Studies indicate that FMT can increase beneficial bacteria in the gut and help induce remission in patients who haven't responded to other treatments. ^{3 5 6 9 10}

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 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]

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]

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]

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]

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]

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]

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) 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]

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]

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]

Citations

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

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. [2018]

2. England 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. [2022]

3. England 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. [2022]

4. Australia 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. [2020]

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

Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis: A Qualitative Assessment of Patient Perceptions and Experiences. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. [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. China pubmed.ncbi.nlm.nih.gov

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation]. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. [2022]