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

Sponsor

Rima Rachid (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05695261

Collaborator

University of Minnesota (Other)

Enrollment

Location

Arms

48.5

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Allergy, Peanut Peanut Allergy Peanut Hypersensitivity Peanut-Induced Anaphylaxis Food Allergy Food Allergy Peanut	Biological: Microbial Transplantation Therapy Drug: Antibiotic Other: Placebo (in place of MTT) Other: Placebo (in place of antibiotics)	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomized on a 1:1 ratio to receive either MTT with antibiotics or placebo/placebo. The unblinding will occur at the end of the study.Patients will be randomized on a 1:1 ratio to receive either MTT with antibiotics or placebo/placebo. The unblinding will occur at the end of the study.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double blind

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 15, 2023

Anticipated Primary Completion Date :

Jan 11, 2027

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

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.	Biological: Microbial Transplantation Therapy Subjects randomized to the MTT/antibiotic arm will be administered oral MTT capsules over the course of 28 days. Drug: Antibiotic 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.	Other: Placebo (in place of MTT) Subjects randomized to the placebo arm will be administered oral placebo capsules in place of MTT over the course of 28 days. Other: Placebo (in place of antibiotics) Subjects randomized to the placebo arm will receive oral placebo in place of antibiotics for 7 days prior to the MTT administration visit.

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.

Biological: Microbial Transplantation Therapy

Subjects randomized to the MTT/antibiotic arm will be administered oral MTT capsules over the course of 28 days.

Drug: Antibiotic

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.

Other: Placebo (in place of MTT)

Subjects randomized to the placebo arm will be administered oral placebo capsules in place of MTT over the course of 28 days.

Other: Placebo (in place of antibiotics)

Subjects randomized to the placebo arm will receive oral placebo in place of antibiotics for 7 days prior to the MTT administration visit.

Outcome Measures

Primary Outcome Measures

Changes in threshold of peanut reactivity during DBPCFC (<=100 mg to 300 mg peanut protein) [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Has a positive SPT to peanut (≥3mm) and/or a positive peanut-specific IgE >0.35kU/L.
For asthmatic patients, has a Spirometry or Peak Flow with Measurement of FEV1>=80% of predicted
Has a negative urine hCG test if a female participant.
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.
Able to swallow 2 empty capsules size 00.
Able to give informed assent and guardian willing to give informed consent.
Willing and able to participate in the study requirements, including study visits, DBPCFCs, serial stool collection
Willing to undergo telephone or email follow-up to assess for safety and adverse events.

Exclusion Criteria:

Patients with a history of severe anaphylaxis to any food (hypotension requiring vasopressor support, hypoxia requiring mechanical ventilation, or neurological compromise)
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).
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.
Recurrent or chronic infections necessitating frequent systemic (including oral) antibiotic administration.
Patients on chronic systemic immunosuppressive therapies.
Patients who are diagnosed with active, chronic urticaria.
Patients who have received peanut oral immunotherapy within the past 6 months.
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.
Women who are pregnant or breast feeding or planning to get pregnant during the time of the study.
Sexually active female patients who refuse to use contraception from enrollment through the third DBPCFC study visit
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.
Patient with current rheumatologic conditions. Exceptions can be made per PI discretion if illness is not expected to affect allergies or treatment.
Patients with neutropenia <1000 unit of measure?
Patients participating or planning to participate in the next 6 months in interventional research trials. Exceptions can be made per PI discretion.
Patients who have received systemic corticosteroids therapy for 1 week or more over the past 2 months.
Patient with an allergy to Vancomycin or Neomycin