A Randomized, Controlled Trial of Probiotic and Peanut Oral Immunotherapy (PPOIT) in Inducing Tolerance in Hong Kong Children With Peanut Allergy Compared With Oral Immunotherapy (OIT) Alone and With Placebo
Primary Purpose
Peanut Allergy, Food Allergy in Children
Status
Active
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
PEANUT OIT: Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations
PEANUT OIT: Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations
PEANUT PLACEBO: Peanut Placebo is maltodextrin powder with food colouring and peanut essence that has similar appearance, taste and smell to the active product.
Sponsored by
About this trial
This is an interventional treatment trial for Peanut Allergy focused on measuring peanut allergy; oral immunotherapy; sustained unresponsiveness; tolerance
Eligibility Criteria
Inclusion Criteria: Subjects are eligible if they meet all of the following criteria
- Aged between 1 year and 17 years of age;
- >=7kg (the weight considered safe for administration of adrenaline autoinjector (e.g. Jext);
- Ethnic Chinese; and
- Confirmed diagnosis of peanut allergy as defined by a failed double-blind placebo-controlled food challenge (DBPCFC) with peanut and a serum peanut-specific IgE level of at least 0.35 kUA (allergen-specific unit) per liter according to ImmunoCAP (Thermo Fisher Scientific) at screening.
Exclusion Criteria: Subjects are not eligible if they meet any of the following criteria
- History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing >3 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction);
- Severe anaphylaxis during the study entry DBPCFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring >3 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction);
- FEV1 <85% at rest and FEV1/FVC ≤ 85% at rest or ongoing chronic persistent asthma (as per Australian Asthma Foundation guidelines);
- Underlying medical conditions (e.g. cardiac disease) that increase the risks for anaphylaxis;
- Use of beta-blockers, and ACE inhibitors;
- Inflammatory intestinal conditions, indwelling catheters, gastrostomies, immunocompromised states, post-cardiac and/or gastrointestinal tract surgery, critically-ill or other conditions that may increase the risks of probiotic associated sepsis;
- Already taking probiotic supplements or foods containing probiotics within the past month;
- Reacting to the placebo component during the study entry DBPCFC;
- Have received other food immunotherapy treatment in the preceding 12 months;
- History of suspected or biopsy-confirmed eosinophilic esophagitis (EoE);
- Currently taking immunomodulatory therapy (including allergen immunotherapy);
- Past or current major illness that in the opinion of the Site Investigator may affect the subject's ability to participate in the study e.g. increased risk to the participant;
- Subjects who in the opinion of the Site Investigator are unable to follow the protocol;
- Another family member already enrolled in the trial (to maintain safety and blinding); or
- Non-English and non-Chinese speaking participants and their families. NOTE: participants with other food allergies are NOT excluded from participating in this trial.
Sites / Locations
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital
- Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital
- Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong
- Department of Paediatrics, Queen Elizabeth Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Probiotic and Peanut Oral Immunotherapy (PPOIT)
Placebo Probiotic and Peanut Oral Immunotherapy
Placebo Probiotic and Placebo Oral Immunotherapy
Arm Description
Probiotic and peanut oral immunotherapy taken daily for 18 months
Placebo probiotic and peanut oral immunotherapy taken daily for 18 months
Placebo probiotic and placebo oral immunotherapy taken daily for 18 months
Outcomes
Primary Outcome Measures
Proportion of participants with 8-week sustained unresponsiveness (passed T1 and T2 challenges) in PPOIT vs placebo
Secondary Outcome Measures
Proportion of participants with 8-week sustained unresponsiveness (passed T1 and T2 challenges) in PPOIT vs peanut OIT.
Proportion of participants who achieve full desensitisation (passed T1 challenge) in: (i) PPOIT vs placebo and (ii) PPOIT vs OIT; and (iii) OIT vs placebo.
The cumulative dose tolerated during the T1 challenge in: (i) PPOIT vs placebo and (ii) PPOIT vs OIT; and (iii) OIT vs placebo.
Cumulative doses below the reaction-eliciting dose if there is a reaction; or total cumulative challenge dose if there is no reaction
Peanut SPT wheal size and peanut and peanut component (Ara h 1, Ara h 2, Ara h 3) sIgE and sIgG4 levels in: (i) PPOIT vs placebo; (ii) PPOIT vs OIT; and (iii) OIT vs placebo and their correlation with sustained unresponsiveness.
Exposure-adjusted incidence rate and severity of treatment emergent adverse events (TEAEs) in (i) PPOIT vs placebo; and (ii) PPOIT vs OIT; and (iii) OIT vs placebo groups.
Full Information
NCT ID
NCT05165329
First Posted
December 8, 2021
Last Updated
October 19, 2022
Sponsor
Chinese University of Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT05165329
Brief Title
A Randomized, Controlled Trial of Probiotic and Peanut Oral Immunotherapy (PPOIT) in Inducing Tolerance in Hong Kong Children With Peanut Allergy Compared With Oral Immunotherapy (OIT) Alone and With Placebo
Official Title
A Randomised, Controlled Trial Evaluating the Effectiveness of Probiotic and Peanut Oral Immunotherapy (PPOIT) in Inducing Desensitisation or Remission in Chinese Children With Peanut Allergy Compared With Oral Immunotherapy (OIT) Alone and With Placebo
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 11, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
At present there is no cure for food allergy. People with a food allergy need to avoid the food they are allergic to in order to stay safe. However we know that accidental exposure is common. Researchers have begun to look at the effectiveness of 'oral immunotherapy' as a treatment for food allergy but results have been mixed.
This study is a randomized controlled trial to evaluate the effectiveness of Probiotic and Peanut Oral Immunotherapy (PPOIT) in inducing tolerance in children with peanut allergy compared with Oral Immunotherapy (OIT) alone and with Placebo. Children will take increasing doses of peanut protein and a set amount of probiotic until a total of 18 months treatment is completed. Children will be tested for peanut allergy at the start of the study, at the end of PPOIT treatment T1 (18 months) and T2 (8 weeks) and T3 (1year) after treatment.
Detailed Description
This is a three-armed, randomised (4:4:1), stratified (by age), blinded, placebo-controlled, parallel-group, superiority trial.
PPOIT Probiotic and peanut OIT taken daily for 18 months.
OIT Probiotic placebo and peanut OIT taken daily for 18 months.
Placebo Probiotic placebo and OIT placebo taken daily for 18 months.
The study consists of:
Screening visit occurs within three months before Day 1.
Day 1 Rush Induction Phase is the start of treatment where participants receive increasing doses of peanut (or placebo) OIT every 20 minutes to reach a final dose of 12mg of peanut protein (or placebo). A single dose of 2x10^10 cfu Lactobacillus rhamnosus GG (or placebo) is also taken.
Week 1 - 16 is the Buildup Phase where the daily dose of peanut (or placebo) OIT is increased every 2 weeks* until a maintenance dose of 2000mg peanut protein (or placebo) is reached. This is expected to take 16 weeks. A fixed daily dose of 2x10^10 cfu Lactobacillus rhamnosus GG (or placebo) is taken during this phase.
* In unavoidable circumstances i.e. school camps, examinations, when scheduling must be amended depending on parents/ participants availability, the window for buildup visits can be +/- 7 days.
Week 16 - 78 is the Maintenance Phase where participants take a daily dose of 2g of peanut protein (or placebo) and a daily dose of 2x10^10 cfu Lactobacillus rhamnosus GG (or placebo) at home and continue until a total of 18 months of treatment is completed.
Week 78 - 86 is the Elimination Phase where participants continue on a peanut-elimination diet post-treatment.
Week 86 -130 is the Monitoring Phase: All groups will be followed up for 12 months after the treatment period. During this time, at 6 months, a telephone interview will be conducted with the participant's parent or guardian to collect information on exposure to peanut/amount of peanut being eaten and allergic reactions.
The primary outcome analysis will be conducted when all subjects have either completed the T2 DBPCFC or terminated the study prior to their T2 visit. Analysis of safety and tolerability, and other secondary outcomes to the T2 timepoint will also be conducted at this time. A supplemental analysis will be conducted at the end of study (i.e. when last subject completes T3 or has withdrawn from the study prior to their T3 visit, or sponsor terminates the study), using cumulative data from the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peanut Allergy, Food Allergy in Children
Keywords
peanut allergy; oral immunotherapy; sustained unresponsiveness; tolerance
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Probiotic and Peanut Oral Immunotherapy (PPOIT)
Arm Type
Active Comparator
Arm Description
Probiotic and peanut oral immunotherapy taken daily for 18 months
Arm Title
Placebo Probiotic and Peanut Oral Immunotherapy
Arm Type
Active Comparator
Arm Description
Placebo probiotic and peanut oral immunotherapy taken daily for 18 months
Arm Title
Placebo Probiotic and Placebo Oral Immunotherapy
Arm Type
Placebo Comparator
Arm Description
Placebo probiotic and placebo oral immunotherapy taken daily for 18 months
Intervention Type
Combination Product
Intervention Name(s)
PEANUT OIT: Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations
Intervention Description
PROBIOTIC: The probiotic to be used is Lactobacillus rhamnosus GG, supplied as a freeze-dried powder. Probiotic will be prepared under strict Food Manufacturing Regulations. The daily dose of 2x10^10 cfu will be packed individually in sachets. Participants will be instructed to mix one scoop of the probiotic in water at a temperature NOT exceeding 38 degrees Celsius. The probiotic must be stored at 4 degrees Celsius
Intervention Type
Combination Product
Intervention Name(s)
PEANUT OIT: Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations
Intervention Description
PROBIOTIC PLACEBO: Probiotic Placebo is maltodextrin. The daily dose will be measured using a standardised scoop. Participants will be instructed to mix one scoop of the probiotic in water at a temperature NOT exceeding 38 degrees Celsius. The probiotic should be stored at 2-8 degrees Celsius.
Intervention Type
Combination Product
Intervention Name(s)
PEANUT PLACEBO: Peanut Placebo is maltodextrin powder with food colouring and peanut essence that has similar appearance, taste and smell to the active product.
Intervention Description
PROBIOTIC PLACEBO: Probiotic Placebo is maltodextrin. The daily dose will be measured using a standardised scoop. Participants will be instructed to mix one scoop of the probiotic in water at a temperature NOT exceeding 38 degrees Celsius. The probiotic should be stored at 2-8 degrees Celsius.
Primary Outcome Measure Information:
Title
Proportion of participants with 8-week sustained unresponsiveness (passed T1 and T2 challenges) in PPOIT vs placebo
Time Frame
T2 - 8 weeks after final day of maintenance treatment
Secondary Outcome Measure Information:
Title
Proportion of participants with 8-week sustained unresponsiveness (passed T1 and T2 challenges) in PPOIT vs peanut OIT.
Time Frame
T2 - 8 weeks after final day of maintenance treatment
Title
Proportion of participants who achieve full desensitisation (passed T1 challenge) in: (i) PPOIT vs placebo and (ii) PPOIT vs OIT; and (iii) OIT vs placebo.
Time Frame
T1 - One Day after final day of maintenance treatment
Title
The cumulative dose tolerated during the T1 challenge in: (i) PPOIT vs placebo and (ii) PPOIT vs OIT; and (iii) OIT vs placebo.
Description
Cumulative doses below the reaction-eliciting dose if there is a reaction; or total cumulative challenge dose if there is no reaction
Time Frame
T1 - One Day after final day of maintenance treatment
Title
Peanut SPT wheal size and peanut and peanut component (Ara h 1, Ara h 2, Ara h 3) sIgE and sIgG4 levels in: (i) PPOIT vs placebo; (ii) PPOIT vs OIT; and (iii) OIT vs placebo and their correlation with sustained unresponsiveness.
Time Frame
At 12 months of treatment; T1 - One Day after final day of maintenance treatment. T2 - 8 weeks after final day of maintenance treatment
Title
Exposure-adjusted incidence rate and severity of treatment emergent adverse events (TEAEs) in (i) PPOIT vs placebo; and (ii) PPOIT vs OIT; and (iii) OIT vs placebo groups.
Time Frame
TEAEs will be collected until T2 - 8 weeks after final day of maintenance.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects are eligible if they meet all of the following criteria
Aged between 1 year and 17 years of age;
>=7kg (the weight considered safe for administration of adrenaline autoinjector (e.g. Jext);
Ethnic Chinese; and
Confirmed diagnosis of peanut allergy as defined by a failed double-blind placebo-controlled food challenge (DBPCFC) with peanut and a serum peanut-specific IgE level of at least 0.35 kUA (allergen-specific unit) per liter according to ImmunoCAP (Thermo Fisher Scientific) at screening.
Exclusion Criteria: Subjects are not eligible if they meet any of the following criteria
History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing >3 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction);
Severe anaphylaxis during the study entry DBPCFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring >3 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction);
FEV1 <85% at rest and FEV1/FVC ≤ 85% at rest or ongoing chronic persistent asthma (as per Australian Asthma Foundation guidelines);
Underlying medical conditions (e.g. cardiac disease) that increase the risks for anaphylaxis;
Use of beta-blockers, and ACE inhibitors;
Inflammatory intestinal conditions, indwelling catheters, gastrostomies, immunocompromised states, post-cardiac and/or gastrointestinal tract surgery, critically-ill or other conditions that may increase the risks of probiotic associated sepsis;
Already taking probiotic supplements or foods containing probiotics within the past month;
Reacting to the placebo component during the study entry DBPCFC;
Have received other food immunotherapy treatment in the preceding 12 months;
History of suspected or biopsy-confirmed eosinophilic esophagitis (EoE);
Currently taking immunomodulatory therapy (including allergen immunotherapy);
Past or current major illness that in the opinion of the Site Investigator may affect the subject's ability to participate in the study e.g. increased risk to the participant;
Subjects who in the opinion of the Site Investigator are unable to follow the protocol;
Another family member already enrolled in the trial (to maintain safety and blinding); or
Non-English and non-Chinese speaking participants and their families. NOTE: participants with other food allergies are NOT excluded from participating in this trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ting Fan Leung
Organizational Affiliation
Department of Paediatrics, The Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong
City
Hong Kong
Country
Hong Kong
Facility Name
Department of Paediatrics, Queen Elizabeth Hospital
City
Hong Kong
Country
Hong Kong
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.allergycuhk.org/ppoit-hk
Description
Related Info
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A Randomized, Controlled Trial of Probiotic and Peanut Oral Immunotherapy (PPOIT) in Inducing Tolerance in Hong Kong Children With Peanut Allergy Compared With Oral Immunotherapy (OIT) Alone and With Placebo
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