Microbiota Transplantation for Peanut Allergy

Overseen By Ghinwa Al Hassanieh

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Rima Rachid

Must not be taking: Immunosuppressants, Omalizumab, Dupilumab, Corticosteroids

Disqualifiers: Severe anaphylaxis, Chronic infections, GI conditions, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II randomized double-blind placebo-controlled trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in peanut allergic patients. In this research the investigators would like to learn more about ways to treat peanut allergies. The primary objective is to evaluate whether MTT with antibiotic pretreatment can increase the threshold of peanut reactivity during a double-blind placebo-controlled food challenge from \<=100 mg peanut protein to 300 mg after 28 days of MTT /placebo therapy and 4 months post therapy initiation.

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 chronic systemic immunosuppressive therapies or have received certain allergy treatments recently, you may not be eligible to participate.

What data supports the effectiveness of the treatment for peanut allergy?

Research shows that fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infections and is being explored for other conditions, suggesting potential for broader applications. Encapsulated FMT has been found to be as effective as other delivery methods, indicating its promise as a treatment option. ^{1 2 3 4 5}

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

Fecal microbiota transplantation (FMT) has been studied for various conditions, and while it shows promise, there are still concerns about adverse events (unwanted side effects). Safety measures like donor screening and careful processing are important to minimize risks. ^{1 2 6 7 8}

How does the treatment Microbiota Transplantation for Peanut Allergy differ from other treatments for this condition?

Microbiota Transplantation for Peanut Allergy is unique because it involves transferring beneficial bacteria from a healthy donor to the patient, potentially altering the gut microbiome to help manage peanut allergies. This approach is different from traditional oral immunotherapy, which focuses on gradually increasing exposure to the allergen itself. ^{9 10 11 12 13}

Research Team

Rima Rachid, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for people with a confirmed peanut allergy who react to small amounts of peanut protein. They must be able to swallow capsules, agree to birth control if applicable, and not have certain chronic illnesses or recent treatments that affect the immune system. Pregnant women and those not using contraception are excluded.

Inclusion Criteria

For asthmatic patients, has a Spirometry or Peak Flow with Measurement of FEV1>=80% of predicted

I am willing to be contacted by phone or email for follow-up.

Develop dose limiting symptoms to peanut during a DPBCFC conducted in accordance with PRACTALL guidelines

Exclusion Criteria

I am a sexually active woman not using birth control.

Patients who have received peanut oral immunotherapy within the past 6 months

I am on long-term medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Antibiotic Pretreatment

Participants receive oral antibiotics or placebo for 7 days to modulate gastrointestinal microbiota

1 week

1 visit (in-person)

MTT/Placebo Treatment

Participants receive MTT or placebo capsules under medical supervision, followed by daily administration for 27 days

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including DBPCFC and gut microbiota analysis

6 months

3 visits (in-person)

Treatment Details

Interventions

• Antibiotic
• Oral Encapsulated Microbiota Transplantation Therapy

Trial Overview The study tests if fecal microbial transplantation (MTT) therapy with prior antibiotic treatment can help increase tolerance to peanuts in allergic patients. Participants will either receive MTT or placebo capsules and their reaction threshold will be tested before and after the treatment period.

Participant Groups

Group I: antibiotic / MTT Experimental Treatment 2 Interventions

Study subjects randomized to the experimental arm will receive oral antibiotics for 7 days as a way to modulate the composition of the gastrointestinal microbiota. Upon completion of oral antibiotics, subjects randomized to the experimental arm will be administeredf MTT under medical supervision. Subjects will be monitored and then discharged. Subjects will be instructed to take MTT capsules daily for 27 days.

Group II: placebo / placebo Active Control 2 Interventions

Study subjects randomized to the placebo arm will receive oral placebo capsules instead of oral antibiotics, for 7 days, at the same frequency and capsule amount per dose. Upon completion of 7 days of placebo (matching the antibiotics given in the experimental arm), subjects randomized to the placebo arm will be administered capsules of placebo (matching the MTT capsules given in the experimental arm) under medical supervision. Subjects will be monitored and then discharged. Subjects will be instructed to take placebo capsules daily for 27 days.

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

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Who Is Running the Clinical Trial?

Rima Rachid

Lead Sponsor

Trials

2

Recruited

40+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Findings from Research

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) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

Encapsulated faecal microbiota transplantation (FMT) is a highly effective and safe treatment for recurrent Clostridioides difficile infection (rCDI), achieving cure rates of 85% after a single course and 93% after multiple courses, based on a systematic review of 35 studies involving 960 patients.

The efficacy of encapsulated FMT for rCDI remains consistent despite variations in treatment protocols, donor screening, and capsule preparation, indicating that this method is as effective as traditional FMT delivery routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy. Cold, F., Baunwall, SMD., Dahlerup, JF., et al.[2022]

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]

In a pilot study involving nine patients with collagenous colitis, fecal microbiota transfer (FMT) showed some improvement in symptoms, particularly in reducing diarrhea and enhancing quality of life, although it did not significantly reduce the number of watery stools overall.

FMT was safe, with no serious adverse events reported, and it appeared to activate the mucosal immune system, as indicated by an increase in lamina propria lymphocytes, suggesting potential benefits for a specific subset of patients with collagenous colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis. Holster, S., Rode, J., Bohr, J., et al.[2021]

Capsulized autologous faecal microbiota transplantation (FMT) was found to be safe and well tolerated in a study of 24 healthy volunteers, with no serious side effects reported during the treatment.

While both the FMT and placebo groups showed improvements in general and intestinal health after antibiotic treatment, there was no significant difference in the time it took for participants to normalize their intestinal habits, indicating that FMT did not provide additional benefits over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial. Stefansson, M., Bladh, O., Flink, O., et al.[2023]

Fecal microbiota transplantation (FMT) is being explored as a treatment for various health conditions, highlighting its potential therapeutic benefits.

The FDA is focused on ensuring the safety of FMT products through rigorous donor screening and manufacturing processes, which is crucial for conducting safe clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory Considerations for Fecal Microbiota Transplantation Products. Carlson, PE.[2020]

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]

In a study of 17 children undergoing peanut oral immunotherapy over approximately 40 weeks, successful desensitization was associated with increased diversity in the oral microbiome and a significant rise in the abundance of Actinobacteria.

Post-therapy, there were trends indicating higher levels of fecal short chain fatty acids, which may play a role in modulating allergic responses and providing protective effects during the desensitization process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights into Microbiome and Metabolic Signatures of Children Undergoing Peanut Oral Immunotherapy. Blackman, AC., Thapa, S., Venkatachalam, A., et al.[2022]

A Phase IIb trial (PPOIT-003) is set to evaluate the effectiveness of a novel treatment combining the probiotic Lactobacillus rhamnosus with peanut oral immunotherapy (PPOIT) in inducing sustained unresponsiveness (SU) in children with peanut allergies, involving 200 participants aged 1 to 10 years.

The study aims to compare the proportion of children achieving SU after 18 months of treatment in the PPOIT group versus both a placebo group and a peanut OIT alone group, with results expected to provide insights into a potential long-term treatment for peanut allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study). Chebar Lozinsky, A., Loke, P., Orsini, F., et al.[2021]

Peanut oral immunotherapy (OIT), including the FDA-approved product Palforzia, has shown promising results in clinical trials, with most participants achieving desensitization to peanuts and some experiencing sustained unresponsiveness.

While peanut OIT can improve quality of life for those with peanut allergies, it carries risks of serious allergic reactions, highlighting the need for further research on its long-term effectiveness and safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peanut Oral Immunotherapy: a Current Perspective. Patrawala, M., Shih, J., Lee, G., et al.[2020]

In a study involving 201 children with peanut allergies, both peanut oral immunotherapy (OIT) and probiotic-enhanced peanut oral immunotherapy (PPOIT) were effective in achieving sustained unresponsiveness, with 46% and 51% of participants respectively, compared to only 5% in the placebo group.

While the addition of the probiotic did not enhance the efficacy of OIT, it may provide a safety benefit, as PPOIT showed a lower incidence of treatment-related adverse events compared to OIT alone, particularly in younger children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. Loke, P., Orsini, F., Lozinsky, AC., et al.[2022]

Oral immunotherapy (OIT) has been shown to effectively increase the threshold of reactivity to peanuts and other food allergens, improving patients' quality of life, as evidenced by numerous studies and meta-analyses.

While OIT can cause common adverse events during treatment, serious reactions are rare, and most patients are willing to continue treatment due to the potential benefits of protection against accidental allergen exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral immunotherapy for peanut allergy: The pro argument. Chinthrajah, RS., Cao, S., Dunham, T., et al.[2020]

References

1. 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]

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

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy. [2022]

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

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

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

Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis. [2021]

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

Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial. [2023]

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

Regulatory Considerations for Fecal Microbiota Transplantation Products. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Faecal microbiota transplantation: establishment of a clinical application framework. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Insights into Microbiome and Metabolic Signatures of Children Undergoing Peanut Oral Immunotherapy. [2022]

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

Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study). [2021]

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

Peanut Oral Immunotherapy: a Current Perspective. [2020]

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

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. [2022]

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

Oral immunotherapy for peanut allergy: The pro argument. [2020]