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Oral immunotherapy (OIT) is a food allergy treatment where small amounts of the food a child is allergic to is eaten and gradually increased over time with the aim to be able to eat a certain amount of the allergen without experiencing an allergic reaction. While this process works in many children there are concerns about safety, feasibility and drop-outs and how to adapt protocols for multiple allergies.
Many OIT trials have targeted approximately 4000mg of single food/day. In these trials up to 40% drop-out. There is evidence much lower doses can have beneficial effects.
The investigators will evaluate if low doses of foods can allow for OIT to multiple foods. This approach may have efficacy against accidental exposure and be able to demonstrate immune changes. This approach may have a low burden of treatment and a low rate of allergic reactions and
This is a single-arm, open label, study of the intervention of low dose multiple-nut OIT in nut allergic children.
After meeting eligibility criteria, participants will have a food challenge to 2-5 nuts.
If the oral food challenge is positive, participants will be enrolled in the study to multiple nut OIT. A blood draw and quality of life (QOL) survey will occur at baseline.
Participants will have dose escalation visits of the multiple nut OIT every 2 months to a target dose of 30mg of each nut protein. A blood draw and QOL survey will occur at 6 months.
Participants will then continue with daily ingestion of the 30mg of each nut protein for 1 year with visits every 3 months.
After 18 months from the start of the study, another oral food challenge will be given to participants to assess the change in the maximum tolerated dose of nuts. A blood draw will assess changes in the immune parameters. A QOL survey will occur at 18 months to assess changes in QOL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| multi-OIT | Experimental | Low dose OIT with multiple allergens |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| multi-OIT | Other | low dose OIT to multiple foods |
|
| Measure | Description | Time Frame |
|---|---|---|
| Desensitization to allergic food as assessed by change in maximum tolerated dose in a dichotomous manner | Change in how much nuts the participant can eat without an allergic reaction after the low dose OIT assessed as dichotomous did the participant reach 5 times the baseline eliciting dose | month 0, month 18 |
| Immunological change in IgG4 | Change in allergen specific immunoglobulin G4 (IgG4) from baseline to end | month 0, month 18 |
| Measure | Description | Time Frame |
|---|---|---|
| Desensitization to allergic food as assessed by change in maximum tolerated dose on a linear scale | A continuous variable amount tolerated at baseline vs at end | month 0, month 18 |
| Immunological change in IgG4 |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility analysis as assessed by can the patients achieve the maintenance dosing of the allergen mix for OIT | Proportion who achieve maintenance doses of their allergen mix (descriptive) | month 18 |
| Feasibility analysis as assessed by drop-out rate |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Julia Upton | The Hospital for Sick Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital for Sick Children | Toronto | Ontario | M5G1X8 | Canada |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 13, 2018 | Nov 20, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005512 | Food Hypersensitivity |
| ID | Term |
|---|---|
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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Change in IgG4 from measures from historical data to 18 month of study. Some patients will have historical IgG4 values to compare
| pre-study, month 18 |
| Desensitization to allergic food as assessed by maximum tolerated dose | Did they reach 300mg (cumulative) on the 18 month exit oral food challenge | month 18 |
| Desensitization to allergic food as assessed by maximum tolerated dose | Did they reach 140mg (cumulative) on the 18 month exit oral food challenge | month 0, month 18 |
Proportion who drop-out of the study (descriptive)
| month 18 |
| Incidence of Treatment-Emergent Adverse Events: Safety analysis as assessed by use of epinephrine | Administration of epinephrine; (descriptive); | month 18 |
| Quality of life scale | Change in quality of life at 18m of children compared to baseline assessment (using validated questionnaire: Food allergy quality of life questionnaires (FAQLQ) FAQLQ Parental form (PF) for ages 0-12 OR the FAQLQ-teenager form (TF) using total score. The FAQLQ total and domain scores range from 1-7 with higher scores indicative of worse health related quality of life with the total score being the average of the domain scores. The domains include Emotional Impact, Social and Dietary Restrictions, Food Anxiety, Allergen Avoidance, and Risk of Accidental Exposure. | month 0, month 18 |
| Change in allergen specific IgE, and components | Change in allergen specific IgE, and components via microarray | month 0, month 18 |
| Basophil activation test | Basophil activation test | month 0, month 18 |
| Skin prick test (SPT) reactivity to the individual nut extracts | The size of the skin prick test will be compared | month 0, month 18 |
| High content functional immune profiling via mass cytometry and single cell sorting | Compare the change in the immune pattern | pre-study, month 18 |
| Number of participants with treatment related adverse effects | Diaries will be analyzed for allergic symptoms and tabulated | month 0, month 18 |