Microbiota Transplantation for Peanut Allergy

Recruiting at 1 trial location

Overseen By Andrew Xuan

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

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat peanut allergies using microbiota transplantation therapy (MTT). Researchers aim to determine if this treatment can help individuals tolerate more peanut protein without allergic reactions. Participants will take capsules containing healthy gut bacteria to assess whether it increases their peanut tolerance. The trial seeks young individuals, aged 12-17, who have a peanut allergy and experience symptoms with small amounts of peanut. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

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

Research is investigating oral encapsulated microbiota transplantation therapy (MTT) to determine its safety and effectiveness for treating peanut allergies. Earlier studies have examined how well people tolerate this treatment. These studies suggest that MTT might alter gut bacteria to improve food tolerance.

Although specific details about side effects from these trials aren't provided, the treatment's Phase 2 status indicates some earlier evidence of safety. This suggests potential safety, but it is not yet certain. In Phase 2, researchers closely monitor for any negative reactions to ensure safety before proceeding to larger trials.

Overall, MTT is under careful study to ensure its safety for people with peanut allergies. Participants in a trial will receive medical supervision to monitor for any potential issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Microbiota Transplantation Therapy for peanut allergy because it offers a novel way to potentially alter the body's immune response to allergens. Unlike standard treatments that focus on managing symptoms with antihistamines or steroids, this approach involves transferring healthy gut bacteria through oral capsules to change the gut microbiome. This method could retrain the immune system to tolerate peanuts, addressing the root cause rather than just alleviating symptoms. Additionally, the use of antibiotics beforehand to prepare the gut is a unique step that may enhance the effectiveness of this therapy, making it a promising option for those with peanut allergies.

What evidence suggests that oral encapsulated microbiota transplantation therapy could be effective for peanut allergy?

Research has shown that Oral Encapsulated Microbiota Transplantation Therapy (MTT), which participants in this trial may receive, might help people with peanut allergies. In one study, 40% of participants tolerated more peanut protein, progressing from reacting to very small amounts (100 mg or less) to handling more without problems. Another study found that transferring healthy gut bacteria from infants to mice prone to allergies protected the mice from severe allergic reactions. These findings suggest that MTT could be a promising way to manage peanut allergies by improving the body's ability to handle peanuts. ^{1 2 3 5 6}

Who Is on the Research Team?

Rima Rachid, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: PART B: open label antibiotic / MTT Experimental Treatment 3 Interventions

In Part B will enroll 13 participants who are peanut allergic and are on maintenance peanut oral immunotherapy (OIT). Participants will undergo an open label food challenge (OFC) up to 2,000 mg peanut protein. These participants will be pre-treated with open label oral Vancomycin and Neomycin over 7 days prior to receiving open label MTT. This part of the study is not randomized or double blind.

Group II: PART A: 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 III: PART A: 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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. foodallergyfund.org foodallergyfund.org/research-1/mtt

A Phase II Trial Evaluating the Safety and Efficacy ... The results were very promising, showing that 40% of patients increased their threshold of reactivity from 100 mg of peanut protein or less (<=1 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05695261

NCT05695261 | Evaluating the Safety and Efficacy of Oral ... This is a phase II trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in peanut ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02960074

NCT02960074 | Evaluating the Safety and Efficacy of Oral ... This is a Phase I trial to evaluate the safety and efficacy of oral encapsulated fecal microbiota transplantation (FMT) in the treatment of peanut allergy.

4. foodallergyfund.org foodallergyfund.org/research-1/evaluating-the-safety-and-efficacy-of-oral-encapsulated-fecal-microbiota-transplant

Evaluating the Safety and Efficacy of Oral Encapsulated ... The research team found that transplanting fecal bacteria from healthy infants into allergy-prone mice protected the mice from anaphylaxis.

5. childrenshospital.org childrenshospital.org/clinical-trials/nct05695261

NCT05695261 This is a phase II trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in peanut ...

6. trials.foodallergy.org trials.foodallergy.org/trials/NCT02960074

Evaluating the Safety and Efficacy of Oral Encapsulated Fecal ... This is a Phase I trial to evaluate the safety and efficacy of oral encapsulated fecal microbiota transplantation (FMT) in the treatment of peanut allergy.