Peanut Allergy
Conditions
Keywords
Peanut Allergy, Peanut Hypersensitivity
Brief summary
Peanut allergy is one of the most serious food allergies because of its life long persistence, and the potential for severe allergic reactions. Effective oral immunotherapy would benefit patients by reducing the likelihood that they will have life-threatening accidental allergic reactions. This research study is being done to develop an effective oral immunotherapy treatment for patients with peanut allergy.
Detailed description
Our hypothesis is that chronic antigen exposure during peanut oral immunotherapy (OIT) will induce beneficial changes in the specific immune response, including: 1) anergy of IgE effector immune cells (e.g., mast cells, basophils) resulting in clinical desensitization; 2) induction of de novo, long lived (memory) B cell responses that antagonize specific IgE and confer immune tolerance. The investigators will test this hypothesis in the following specific aims: 1. Induce desensitization in peanut allergic subjects with peanut OIT and evaluate the safety of the peanut OIT desensitization protocol. 2. Induce long-standing tolerance in peanut allergic subjects with maintenance peanut OIT and evaluate the efficacy of allergen-specific testing to predict tolerance. 3. Longitudinally evaluate basophil and mast cell reactivity in subjects receiving peanut OIT and their relationship to the induction of desensitization. 4. Longitudinally evaluate the allergen-specific B-cell repertoire in subjects receiving peanut OIT and its relationship to the induction of tolerance.
Interventions
DRUGPeanut flour OIT
Patients will receive daily escalating dosages (Peanut flour OIT) as determined in the modified rush phase as stated in the protocol. The dosage will be escalated until a daily dose of 4000 mg is reached. A Double-blind, placebo-controlled food challenge will then consist of two challenges performed on the same day. One challenge will consist of 7 doses of peanut given every 10-20 minutes in increasing amounts up to a total of 10 grams of whole peanut (5 grams of peanut protein) masked by inclusion in vehicle food. The other challenge will consist of placebo material given similarly.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
The observational control arm (parallel for the first year) was then offered to cross over to active treatment
Eligibility
Sex/Gender
ALL
Age
7 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of peanut allergy by a positive prick skin test to peanut (\> 8 mm reaction wheal) or CAP FEIA \>10 and a history of objective clinical symptoms within one hour after ingestion of peanuts 2. Ability to provide informed consent. 3. Males and females of all ethnic/racial groups between 7 and 21 years who are otherwise healthy.
Exclusion criteria
1. Clinical history of a severe anaphylactic reaction known or suspected to be caused by ingestion of peanut that required treatment with 2 or more administrations of epinephrine or hospitalization 2. Moderate to Severe Asthma as defined using the Impairment or Risk Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/) 3. Poorly controlled Asthma as defined using the Control Criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/) 4. Diagnosis of other severe or complicating medical problems 5. Autoimmune or chronic immune or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders 6. Primary Immune Deficiency 7. Use of beta blockers, angiotension converting enzyme inhibitors, or monoamine oxidase inhibitors 8. Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding 9. Use within the past year of other systemic immunomodulatory treatment, including allergen immunotherapy, use of biologics with an immune target, including Xolair
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance or Sustained Unresponsiveness | at least 36 months | The consumption of 5 grams of peanut protein during a double-blind placebo controlled food challenge without objective symptoms after one month of post treatment avoidance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Desensitization | at least 36 months | The consumption of 5 grams of peanut protein during an open food challenge without objective symptoms immediately post treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control - Crossover The subjects enrolled in the observational control group will have follow-up visits every 6 months. Each visit will involve a medical history and physical examination. After year 1, they will have the opportunity to cross over to active therapy. | 4 |
| Peanut OIT Peanut flour OIT: Patients will receive daily escalating dosages as determined in the modified rush phase as stated in the protocol. The dosage will be escalated until a daily dose of 4000 mg is reached. A Double-blind, placebo-controlled food challenge will then consist of two challenges performed on the same day. One challenge will consist of 7 doses of peanut given every 10-20 minutes in increasing amounts up to a total of 10 grams of whole peanut (5 grams of peanut protein) masked by inclusion in vehicle food. The other challenge will consist of placebo material given similarly. | 26 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Withdrawn before any treatment | 0 | 3 |
Baseline characteristics
| Characteristic | Control - Crossover | Peanut OIT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 26 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 23 Participants | 26 Participants |
| Region of Enrollment United States | 4 participants | 26 participants | 30 participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 23 / 23 |
| serious Total, serious adverse events | 0 / 4 | 0 / 23 |
Outcome results
Primary
Tolerance or Sustained Unresponsiveness
The consumption of 5 grams of peanut protein during a double-blind placebo controlled food challenge without objective symptoms after one month of post treatment avoidance
Time frame: at least 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control - Crossover | Tolerance or Sustained Unresponsiveness | 2 Participants |
| Peanut OIT | Tolerance or Sustained Unresponsiveness | 7 Participants |
Secondary
Desensitization
The consumption of 5 grams of peanut protein during an open food challenge without objective symptoms immediately post treatment
Time frame: at least 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control - Crossover | Desensitization | 3 Participants |
| Peanut OIT | Desensitization | 19 Participants |