Food Hypersensitivity
Conditions
Keywords
Peanut allergy
Brief summary
The purpose of this study is to attempt to understand how desensitization works in peanut allergic children who are undergoing oral immunotherapy (OIT) to peanut. We want to identify the early changes in the desensitization process the immune cells undergo to become desensitized to the peanut protein.
Detailed description
Peanut allergic children will undergo an oral food challenge (OFC) to 1 gm peanut protein in order to accomplish two objectives: (1)to confirm the diagnosis of peanut allergy, and (2) to measure the amount of peanut protein it takes to cause an allergic reaction. Each subject will then undergo a modified rush phase in which the subject receives 6 doses of peanut protein in one day. The build-up phase begins afterward in which the subject's dose of peanut protein is increased every 2 weeks for 36 weeks. After the final build-up dose, the subject consumes that dose for 2 weeks after which he or she returns to the food allergy center for the second food challenge. If the subject successfully consumes this food challenge without symptoms, the daily dosing of peanut protein will be stopped and the subject will then undergo a third food challenge. If the subject successfully consumes the peanut protein during that challenge, he or she will return for a fourth food challenge to peanut.
Interventions
DRUGOpen label peanut OIT
Subject will take increasing amounts of peanut protein up to a maximum maintenace dose of 1450mg.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Age 4 to up to 12 years of age of any gender, race, or ethnicity. * Minimum weight 16 kg at the time of enrollment. * Physician diagnosis of peanut allergy OR convincing clinical history of an allergic reaction to peanut. * Detectable serum peanut -specific IgE level (CAP-FEIA ≥ 0.35 kU/L) and a positive SPT (wheal ≥ 3mm on skin prick test to peanut extract compared to a negative control.) * Allergic reaction to ≤ 1 gm peanut protein during a blinded oral challenge test conducted at screening (e.g., a double-blinded, placebo-controlled food challenge \[DBPCFC\]). * Written informed consent from parent/guardian. * Written assent from subject if applicable * Consumption of oat-containing product within 90 days prior to enrollment
Exclusion criteria
* History of allergic reaction to peanut consistent with severe anaphylaxis (defined as hypotension/shock; or neurologic impairment). * Chronic disease other than asthma, atopic dermatitis, rhinitis requiring therapy; e.g., heart disease or diabetes. * Active eosinophilic gastrointestinal disease in the past 2 years * Participation in any interventional study for the treatment of food allergy in the 6 months prior to visit -1 * Inhalant allergen immunotherapy that has not yet reached maintenance dosing. * Asthma defined as moderate or severe persistent by National Asthma Education and Prevention Program Expert Panel Guidelines (e.g. asthma that requires more than fluticasone 440 mcg or its equivalent daily for adequate control). * Inability to discontinue antihistamines for skin testing, OFC and the initial dose escalation. * Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) in the 12 months prior to visit -1. * Any systemic therapy which in the judgment of the investigator could be immunomodulatory (e.g. rituximab) in the 12 months prior to visit -1, Systemic corticosteroid therapy of up to a total of three weeks is allowed. * Use of investigational drug in 90 days prior to visit -1. * Plan to use any investigational drug during the study period. * The presence of any medical condition that the investigator deems incompatible with participation in the trial. * Inability to speak English.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Develop Desensitization | 40 weeks | The percentage of peanut allergic subjects who develop desensitization as defined by being able to consume 5000mg of peanut protein during a double blind food challenge after completing a build-up phase of peanut OIT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Maintain Desensitization Once OIT is Stopped | 4 weeks | The percentage of subjects who maintain desensitization once the OIT is withdrawn at 1, 2, 3, and 4 week intervals. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Wheal Diameter, as Assessed by the Skin Prick Test (SPT) to Peanut | 44 weeks | Allergic reactivity of mast cells is assessed by skin prick testing through measurement of the wheal diameter after exposure to peanut. This outcome measure reports the change in skin prick test wheal diameter from baseline through the end of the treatment period. |
| Change in Peanut Specific Immunoglobin E (IgE) From Baseline Until Desensitization Food Challenge | 44 weeks | The investigation of mechanistic changes that occur in the immune system over the duration of the study - Peanut specific immunoglobin E (IgE) |
| Change in Immunoglobin G4 (IgG4) to Peanut From Baseline Until Desensitization Food Challenge | 44 weeks | The investigation of mechanistic changes that occur in the immune system dover the duration of the study - Immunoglobin G4 (IgG4) to peanut |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Peanut OIT Open label orally ingested peanut flour with maintenance dose of 1450mg | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Open Label Peanut OIT |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 8.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 15 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Percentage of Subjects Who Develop Desensitization
The percentage of peanut allergic subjects who develop desensitization as defined by being able to consume 5000mg of peanut protein during a double blind food challenge after completing a build-up phase of peanut OIT.
Time frame: 40 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Peanut OIT | Percentage of Subjects Who Develop Desensitization | 81.25 percentage of participants |
Secondary
Percentage of Subjects Who Maintain Desensitization Once OIT is Stopped
The percentage of subjects who maintain desensitization once the OIT is withdrawn at 1, 2, 3, and 4 week intervals.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Peanut OIT | Percentage of Subjects Who Maintain Desensitization Once OIT is Stopped | 21.43 percentage of participants |
Other Pre-specified
Change From Baseline in the Wheal Diameter, as Assessed by the Skin Prick Test (SPT) to Peanut
Allergic reactivity of mast cells is assessed by skin prick testing through measurement of the wheal diameter after exposure to peanut. This outcome measure reports the change in skin prick test wheal diameter from baseline through the end of the treatment period.
Time frame: 44 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open Label Peanut OIT | Change From Baseline in the Wheal Diameter, as Assessed by the Skin Prick Test (SPT) to Peanut | -8.8 mm |
Other Pre-specified
Change in Immunoglobin G4 (IgG4) to Peanut From Baseline Until Desensitization Food Challenge
The investigation of mechanistic changes that occur in the immune system dover the duration of the study - Immunoglobin G4 (IgG4) to peanut
Time frame: 44 weeks
Population: Blood work was not able to be obtained from 1 of 16 evaluable subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Peanut OIT | Change in Immunoglobin G4 (IgG4) to Peanut From Baseline Until Desensitization Food Challenge | 3.68 mg/dL of IgG4 |
Other Pre-specified
Change in Peanut Specific Immunoglobin E (IgE) From Baseline Until Desensitization Food Challenge
The investigation of mechanistic changes that occur in the immune system over the duration of the study - Peanut specific immunoglobin E (IgE)
Time frame: 44 weeks
Population: Blood work was not able to be obtained from 1 of 16 evaluable subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Peanut OIT | Change in Peanut Specific Immunoglobin E (IgE) From Baseline Until Desensitization Food Challenge | -19 kU/L of peanut-specific IgE |