Fecal Microbiota Transplant for Ulcerative Colitis

Overseen By Zhi-Dong Jiang, Dr.PH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Antibiotics, Immunosuppressants, Chemotherapy, others

Disqualifiers: Severe UC, Active cancer, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of delivering fecal microbiota transplant (FMT) for individuals with active ulcerative colitis (UC), a condition that inflames the colon. One group will receive FMT through a frozen enema (a solution given through the rectum), while another group will take it as a lyophilized powder (freeze-dried) in capsules. Researchers aim to determine the safety and effectiveness of these treatments and their impact on gut bacteria. Individuals with active UC who have had the condition for some time and can take either an enema or capsules might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken systemic antibiotics within 14 days before the treatment starts or if you are on high doses of certain immune-suppressing drugs like prednisone.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that fecal microbiota transplantation (FMT) is generally safe for treating certain gut problems. Studies have found that FMT can help people with recurring Clostridium difficile infections without major safety issues. This procedure uses gut bacteria from carefully screened healthy donors.

For ulcerative colitis, reports suggest that FMT is well-tolerated and safe. In past studies with ulcerative colitis patients, FMT was considered safe, and most participants handled it well. Researchers have used both frozen and capsule forms of FMT, like those tested in the current trial, and found them safe in previous experiments.

In summary, while more research is needed, existing studies provide some reassurance about the safety of using FMT for people with active ulcerative colitis. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for ulcerative colitis, which typically involve anti-inflammatory drugs and immune system suppressors, PRIM-DJ2727 offers a unique approach by utilizing fecal microbiota transplantation (FMT). This treatment is exciting because it introduces a new way to balance gut bacteria, potentially leading to improved gut health and reduced inflammation. The delivery methods for PRIM-DJ2727 are also innovative, with options including both frozen samples and easy-to-take capsules. These features could make the treatment more accessible and comfortable for patients, offering a promising alternative to current therapies.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that fecal microbiota transplantation (FMT) can help people with ulcerative colitis (UC) who haven't responded to other treatments. One study found that FMT significantly improved symptoms in patients with active UC. Another analysis indicated that FMT could be effective, especially for those whose condition doesn’t improve with standard treatments. In this trial, participants will receive either frozen FMT or capsule FMT. Both methods introduce healthy bacteria into the gut, potentially reducing inflammation and promoting healing. These findings suggest that FMT could be a promising treatment option for UC. ^{2 4 6 7 8}

Who Is on the Research Team?

Herbert L DuPont, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults with active Ulcerative Colitis (UC) who are not pregnant, breastfeeding, or planning pregnancy. They must have a Partial Mayo score ≥ 3 and agree to use birth control. Excluded are those with severe UC, recent antibiotics use, certain infections like HIV/Hepatitis B/C, past FMT or recurrent C. difficile infection within 6 months, compromised immune systems or significant uncontrolled diseases.

Inclusion Criteria

Willing and able to sign an informed consent form and attend all study-related clinic visits, assessments, and follow-up phone calls

Subject has an attending physician who will provide the non-FMT care

My ulcerative colitis is active with a Partial Mayo score of 3 or more.

Exclusion Criteria

I have a history of active gastrointestinal conditions.

History of use of an investigational drug within 90 days prior to the screening visit

I cannot take medicine as an enema or swallow many pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fecal Microbiota Transplantation (FMT) via retention enema or oral capsules

5 weeks

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• PRIM-DJ2727 - CAPSULES
• PRIM-DJ2727 - FROZEN

Trial Overview The study tests the safety and effectiveness of fecal microbiota transplantation (FMT) in treating UC using two methods: frozen FMT via enema and lyophilized powder in capsules. It also examines changes in gut microbiome diversity after treatment.

How Is the Trial Designed?

Group I: Experimental: PRIM-DJ2727 - FROZEN Experimental Treatment 1 Intervention

Group II: Experimental: PRIM-DJ2727 - CAPSULES Experimental Treatment 1 Intervention

PRIM-DJ2727 - CAPSULES is already approved in United States, European Union for the following indications:

Approved in United States as Fecal Microbiota Transplantation (FMT) for:

• Recurrent Clostridioides difficile infection

Approved in European Union as Fecal Microbiota Transplantation (FMT) for:

• Recurrent Clostridioides difficile infection

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 15 patients with steroid-dependent ulcerative colitis (UC), a step-up fecal microbiota transplantation (FMT) strategy led to clinical improvement in 57.1% of patients, allowing them to discontinue steroid use.

The successful treatment was associated with significant changes in gut microbiota composition, resembling that of the donor, and no severe adverse events were reported, indicating the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. Cui, B., Li, P., Xu, L., et al.[2022]

Faecal microbiota transplantation (FMT) is being established as a safe second-line treatment for recurrent Clostridium difficile infections, with a comprehensive framework developed to ensure donor screening and clinical application comply with the European Tissue Act.

The framework includes rigorous donor recruitment and screening processes, laboratory protocols for processing faecal samples, and a structured follow-up system to monitor patient outcomes, ensuring safety and traceability in FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation: establishment of a clinical application framework. Jørgensen, SMD., Hansen, MM., Erikstrup, C., et al.[2022]

Faecal microbiota transplantation (FMT) has shown effectiveness in inducing remission in active ulcerative colitis (UC), with a clinical remission rate of 28% in FMT patients compared to 9% in placebo groups based on a meta-analysis of randomized controlled trials involving 277 patients.

The study found no major short-term safety concerns associated with FMT, suggesting it is a safe option for patients with UC, although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Costello, SP., Soo, W., Bryant, RV., et al.[2022]

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]

In a review of 12 published studies on fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD), only one study suggested a significant donor effect, while the majority showed no statistically significant differences in efficacy based on donor material.

Despite the lack of strong evidence for donor effects, the study highlights that the existing data cannot completely rule out their potential clinical importance, indicating a need for larger, well-designed trials to explore this further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. Olesen, SW., Gerardin, Y.[2021]

In a study involving 7 patients with mild to moderate ulcerative colitis, fecal microbiota transplantation (FMT) achieved a donor similarity index (DSI) of 40-50% in about two-thirds of recipients, indicating some level of microbiota engraftment.

Despite achieving this level of engraftment, only one patient experienced a temporary clinical improvement, suggesting that while FMT can alter the microbiota, its efficacy in achieving lasting remission in ulcerative colitis may require further investigation and optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. Damman, CJ., Brittnacher, MJ., Westerhoff, M., 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]

High-volume fecal microbiota transplantation (FMT) using an endoscopic jejunal application route effectively cured recurrent Clostridium difficile colitis in all cases studied, demonstrating its efficacy as a treatment option.

While the procedure was generally well tolerated, there is a risk of serious complications, such as aspiration pneumonia, which highlights the need for careful monitoring during FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic peroral jejunal fecal microbiota transplantation. Link, A., Lachmund, T., Schulz, C., et al.[2017]

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) 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]

Citations

1. withpower.com withpower.com/trial/phase-1-colitis-3-2023-a9161

Fecal Microbiota Transplant for Ulcerative Colitis Research shows that fecal microbiota transplantation (FMT) can help patients with ulcerative colitis (UC) who haven't responded to other treatments. Studies ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12305158/

Fecal microbiota transplantation: A promising treatment ... Core Tip: Fecal microbiota transplantation shows significant potential in treating chronic liver diseases by improving liver inflammation, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2590097820300239

Long term management of ulcerative colitis with Faecal ... Results with microbiota targeted therapies including probiotics, prebiotics, and antibiotics have however been inconsistent and lack reproducibility. Faecal ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35766805/

A Systematic Review and Meta-Analysis of Double-Blind ... Efficacy of Fecal Microbiota Transplantation in the Treatment of Active Ulcerative Colitis: A Systematic Review and Meta-Analysis of Double ...

5. nature.com nature.com/articles/s41467-020-17180-x

An ecological framework to understand the efficacy of fecal ... ... trial of fecal transplantation for patients ... efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04373473

Evaluation the Safety and Efficacy of Lyophilized Fecal ... Fecal Microbiota Transplantation (FMT) product manufactured as PRIM-DJ2727 capsules consists of lyophilized microbiota suspension from well-screened donors.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7815055/

Evaluation of Six Weekly Oral Fecal Microbiota Transplants ... We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006273/

Fecal microbiota transplantation for patients with ulcerative ... Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile.