Food Hypersensitivity
Conditions
Keywords
Peanut allergy
Brief summary
Peanut allergy is known to cause severe anaphylactic reactions.The goal of this proposal is to produce a new treatment that would benefit young subjects who have recently been diagnosed with peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance).
Detailed description
Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies, it tends to be more persistent and its prevalence seems to be rising. Currently, there is no proven treatment other than strict avoidance. We are attempting to decrease the risk of anaphylaxis on accidental ingestion by desensitizing subjects to peanut using peanut mucosal immunotherapy (PMIT) more commonly called oral immunotherapy (OIT). We are also studying the effect of PMIT on the peanut-specific immune response to determine if tolerance to peanut protein will develop. Based on our preliminary work and recent studies supporting the importance of early oral exposure in tolerance induction, we propose that early treatment of peanut allergy with PMIT will be safe and effective. Children ages 9 to 36 months with peanut allergy will be randomized to receive high or low dose PMIT using peanut flour. Subjects will undergo desensitization on the first day and then increase the doses gradually to a maintenance dose. Doses will be taken daily at home except for dose increases which will be done on the research unit. Subjects will undergo a double-blinded, placebo-controlled food challenge (DBPCFC) if challenge criteria are met. Subjects passing the first challenge will stop PMIT and repeat the DBPCFC to assess tolerance. Outcome variables of interest include response to oral food challenges (OFC), skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G (IgG), and immunoglobin G4 (IgG4) and stool immunoglobin A (IgA), T and B cell responses, quality of life, and adverse events. As secondary and exploratory outcomes, these longitudinal results will be compared between high and low dose PMIT groups and controls using appropriate statistical analysis.
Interventions
Defatted peanut in flour form to be used as treatment for peanut allergy
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
For exploratory analysis, subjects will be randomized 1:1 to high (3000mg) and low dose (300mg) OIT to potentially look for a dose response. Low dose will be masked by adding oat flour to provide a dose equal to high dose with respect to flour but with lower peanut protein content
Intervention model description
For the purposes of the primary outcome, all subjects will receive peanut OIT and represent a single group. For exploratory analysis, subjects will be randomized to high and low dose OIT to potentially look for a dose response.
Eligibility
Sex/Gender
ALL
Age
9 Months to 36 Months
Healthy volunteers
No
Inclusion criteria
* Age 9-36 months of either sex, any race, any ethnicity at the time of the initial visit * EITHER a positive skin prick test to peanuts or in vitro \[CAP-FEIA\] peanut immunoglobin E (IgE) level in the blood \> 0.35 kU/L PLUS a history of a clinical allergic reaction (defined as significant clinical symptoms occurring within 60 minutes after ingesting peanuts) within 6 months of screening * OR a positive prick skin test to peanuts and in vitro \[CAP-FEIA\] peanut IgE level \> 5 kU/L when there is no history of allergic reaction and no known peanut exposure * Provision of signed informed consent * Development of symptoms characteristic of IgE-mediated food allergy (urticaria, angioedema, respiratory distress/wheeze/cough, vomiting/diarrhea, anaphylaxis) during initial oral food challenge
Exclusion criteria
* History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise * Currently participating in a study using an investigational new drug * Participation in any interventional study for the treatment of food allergy in the past 12 months * Subjects with a known wheat food allergy will be excluded because of cross contamination of oat with wheat * Severe atopic dermatitis * Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines * Inability to discontinue antihistamines for skin testing and OFCs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). | After 36 months of OIT dosing followed by 1 month of avoidance | The goal of the study is to treat peanut-allergic subjects with peanut OIT and to determine whether this protocol lowers their risk of anaphylactic reactions and causes SU. We expect to demonstrate the effectiveness of peanut OIT in inducing SU by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT followed by avoidance of therapy for 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). | After 36 months of OIT dosing | We expect to demonstrate the effectiveness of peanut OIT in inducing desensitization by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT . |
| Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT. | After 36 months of OIT dosing followed by 1 month of avoidance | In addition to studying the effectiveness of peanut OIT, we will also determine the safety of peanut OIT by reporting the average rate of TAEs per person per dose. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peanut Oral Immunotherapy All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed ITT. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Peanut Oral Immunotherapy |
|---|---|
| Age, Categorical <=18 years | 37 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 28.5 months |
| Peanut immunoglobin E (IgE) | 14.4 kUA/L |
| Peanut skin prick test (SPT) | 11.5 mm wheal size |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 33 Participants |
| Region of Enrollment United States | 37 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 35 / 37 |
| serious Total, serious adverse events | 0 / 37 |
Outcome results
Primary
Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
The goal of the study is to treat peanut-allergic subjects with peanut OIT and to determine whether this protocol lowers their risk of anaphylactic reactions and causes SU. We expect to demonstrate the effectiveness of peanut OIT in inducing SU by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT followed by avoidance of therapy for 4 weeks.
Time frame: After 36 months of OIT dosing followed by 1 month of avoidance
Population: 37 subjects considered with ITT analysis including 5 withdrawals
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Peanut Oral Immunotherapy | Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). | 29 Participants |
Secondary
Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT.
In addition to studying the effectiveness of peanut OIT, we will also determine the safety of peanut OIT by reporting the average rate of TAEs per person per dose.
Time frame: After 36 months of OIT dosing followed by 1 month of avoidance
Population: 37 subjects considered with ITT analysis including 5 withdrawals
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Peanut Oral Immunotherapy | Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT. | 0.8 AEs per person per dose |
Secondary
Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
We expect to demonstrate the effectiveness of peanut OIT in inducing desensitization by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT .
Time frame: After 36 months of OIT dosing
Population: 37 subjects considered with ITT analysis including 5 withdrawals
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Peanut Oral Immunotherapy | Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). | 30 Participants |