Evaluating the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients

January 23, 2023 updated by: Rima Rachid

A Phase II Trial to Evaluate the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients

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.

Study Overview

Detailed Description

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 24 peanut allergic patients, 12-17 years of age. After reacting to <=100 mg peanut protein during initial DBPCFC, patients will be randomized to receive either oral Vancomycin and Neomycin or placebo/placebo for 7 days. Patients will then come to the Experimental and Therapeutic Unit (ETU) to receive orally 5 capsules of MTT or placebo under medical supervision. Patients will then take 2 capsules of MTT or placebo daily for 27 days. Patients will return to the ETU to undergo a second DBPCFC within 2 weeks of end of MTT/placebo treatment and 4 months post MTT initiation. They will return to the ETU for an exit visit 6 months after end of treatment. Gut microbiota will be analyzed serially using state-of-the-art 16SRNA sequencing prior to transplantation, then at 4 weeks, 4-month, and 6 months post transplantation. Immunological biomarkers and mechanistic studies will be performed on blood taken at baseline, second DBPCFC visit and exit visit. Adverse events will be monitored carefully throughout the study.

Study Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rima Rachid, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Develop dose limiting symptoms to peanut during a DPBCFC conducted in accordance with PRACTALL (Practical Issues in Allergology, Joint United States/European Union Initiative) guidelines at 1 mg, 3 mg, 10 mg, 30 mg, or 100 mg peanut protein.
  2. Has a positive SPT to peanut (≥3mm) and/or a positive peanut-specific IgE >0.35kU/L.
  3. For asthmatic patients, has a Spirometry or Peak Flow with Measurement of FEV1>=80% of predicted
  4. Has a negative urine hCG test if a female participant.
  5. Agrees to use an acceptable single-barrier form of birth control from enrollment through the exit DBPCFC study visit if female of childbearing potential and sexually active. An example of a single-barrier method of contraception includes condoms or oral contraceptives. Acceptable methods of birth control include implants, injectables, combined oral contraceptives, some intrauterine contraceptive devises (IUDs), sexual abstinence, a vasectomized partner, the contraceptive patch, the contraceptive ring, and condoms.
  6. Able to swallow 2 empty capsules size 00.
  7. Able to give informed assent and guardian willing to give informed consent.
  8. Willing and able to participate in the study requirements, including study visits, DBPCFCs, serial stool collection
  9. Willing to undergo telephone or email follow-up to assess for safety and adverse events.

Exclusion Criteria:

  1. Patients with a history of severe anaphylaxis to any food (hypotension requiring vasopressor support, hypoxia requiring mechanical ventilation, or neurological compromise)
  2. Patients with a history of IgE mediated reactions to food (excluding allergic reactions to peanut, tree nuts, egg and milk, provided that MTT does not contain traces of these l food estimated to be above the LOAEL in 5 capsules combined, and excluding oral allergy syndrome).
  3. Patients with chronic illness other than controlled asthma that is mild intermittent, mild- persistent or moderate persistent, mild eczema and allergic rhinitis. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
  4. Recurrent or chronic infections necessitating frequent systemic (including oral) antibiotic administration.
  5. Patients on chronic systemic immunosuppressive therapies.
  6. Patients who are diagnosed with active, chronic urticaria.
  7. Patients who have received peanut oral immunotherapy within the past 6 months.
  8. Patients who are on the up-dosing phase of aeroallergen immunotherapy or patients who have received Omalizumab or dupilumab therapy within the past 6 months.
  9. Women who are pregnant or breast feeding or planning to get pregnant during the time of the study.
  10. Sexually active female patients who refuse to use contraception from enrollment through the third DBPCFC study visit
  11. Patient with GI conditions including inflammatory bowel disease, eosinophilic esophagitis, food protein induced enterocolitis, uncontrolled reflux despite medication, uncontrolled chronic constipation despite medication, esophageal dysmotility, swallowing dysfunction, delayed gastric emptying syndromes, pill esophagitis or history of aspiration pneumonia within 3 months prior to screening.
  12. Patient with current rheumatologic conditions. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
  13. Patients with neutropenia <1000 unit of measure?
  14. Patients participating or planning to participate in the next 6 months in interventional research trials. Exceptions can be made per PI discretion.
  15. Patients who have received systemic corticosteroids therapy for 1 week or more over the past 2 months.
  16. Patient with an allergy to Vancomycin or Neomycin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: antibiotic / MTT

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.

Subjects randomized to the MTT/antibiotic arm will be administered oral MTT capsules over the course of 28 days.
Subjects randomized to the MTT/antibiotic arm will receive oral antibiotics for 7 days prior to the MTT administration visit.
Active Comparator: placebo / placebo

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.

Subjects randomized to the placebo arm will be administered oral placebo capsules in place of MTT over the course of 28 days.
Subjects randomized to the placebo arm will receive oral placebo in place of antibiotics for 7 days prior to the MTT administration visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in threshold of peanut reactivity during DBPCFC (<=100 mg to 300 mg peanut protein)
Time Frame: 4 months post MTT
Changes in threshold of peanut reactivity during DBPCFC after 28 days of MTT from <=100 mg to 300 mg peanut protein and 4 months post therapy initiation.
4 months post MTT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in threshold of peanut reactivity during DBPCFC (<=100 mg to 600 mg peanut protein)
Time Frame: 4 months post MTT
Changes in threshold of peanut reactivity during DBPCFC after 28 days of MTT from <=100 mg to 600 mg peanut protein and 4 months post therapy initiation.
4 months post MTT
Adverse Events
Time Frame: 8 months
MTT Treatment emergent adverse events
8 months
Changes in Skin Test Wheal Size and IgE level
Time Frame: 8 months
Changes in skin test peanut specific wheal size, peanut-specific IgE level over time
8 months
Changes in Gut Microbial Composition
Time Frame: 8 months
Changes in gut microbial composition and persistence of that change over time
8 months
Changes in Biomarkers
Time Frame: 8 months
Changes in biomarkers including RoRgt+Treg cells and Th2 helper cells frequencies after MTT therapy
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Rima Rachid, Boston Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 15, 2023

Primary Completion (Anticipated)

January 11, 2027

Study Completion (Anticipated)

March 1, 2027

Study Registration Dates

First Submitted

January 13, 2023

First Submitted That Met QC Criteria

January 13, 2023

First Posted (Actual)

January 23, 2023

Study Record Updates

Last Update Posted (Actual)

January 25, 2023

Last Update Submitted That Met QC Criteria

January 23, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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