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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01AT004435-09 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
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The goal of this study will be to increase the reaction threshold (desensitization) of peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance).
Allergy to peanuts and tree nuts affects approximately 1.4% of the population. Allergic reactions to peanut can be severe and life threatening and account for the vast majority of fatalities due to food-induced anaphylaxis. At present, there are no viable treatment options for patients with peanut allergy. The current standard of care is strict dietary elimination and emergency preparedness with an anaphylaxis kit in the event of an accidental reaction.
Our group and others have shown that oral immunotherapy can provide protection from anaphylaxis to a variety of food proteins. In addition, our ongoing research has demonstrated that sublingual immunotherapy to peanut provides a safe, alternative mode of immunotherapy to reduce allergic reaction rates (desensitization) during oral food challenge (OFC) to peanut. The goal of this study will be to desensitize peanut allergic children using peanut sublingual immunotherapy and to determine if the nonreactive state of the immune system persists after treatment has been discontinued (tolerance). Children ages 1-11 years will be enrolled following an entry double blind, placebo controlled food challenge (DBPCFC).
After at least 48 months of peanut SLIT study drug, subjects will undergo a second DBPCFC to 5000 mg of peanut protein to assess desensitization.
Outcome variables of interest include response to double blind, placebo controlled food challenges, skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G (IgG), and immunoglobin G4 (IgG4) and salivary immunoglobin A (IgA), T and B cell responses, basophil hyporesponsiveness, quality of life, and adverse events.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Peanut ( liquid peanut extract) SLIT | Experimental | All subjects will receive peanut SLIT upon enrollment for at least the first 48 months. After the desensitization DBPCFC after at least 48 months of treatment, subjects will be randomized off treatment from 1 to 17 weeks. Subjects will then undergo another DBPCFC. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liquid peanut extract (Peanut SLIT) | Drug | Liquid peanut extract will be administered under the tongue |
|
| Measure | Description | Time Frame |
|---|---|---|
| Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population | An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 5% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect. | 48 - 52 months |
| Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population | An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 10% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect. | 48-52 months |
| Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half. | A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to reduce by half, also called half-life of sensitivity threshold. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data. | 52 months |
| Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events During the Study. | Number of participants with adverse events (AEs) and serious adverse events (SAEs) during the SLIT treatment portion of the study. | 48 months |
| Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wesley Burks, MD | University of North Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
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Peanut allergic children ages 1-11 years
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| ID | Title | Description |
|---|---|---|
| FG000 | Peanut (Liquid Peanut Extract) SLIT | All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC. Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Peanut ( Liquid Peanut Extract) SLIT | All subjects will receive peanut SLIT upon enrollment for at least the first 48 months. After the desensitization DBPCFC after at least 48 months of treatment, subjects will be randomized off treatment from 1 to 17 weeks. Subjects will then undergo another DBPCFC. Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population | An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 5% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect. | Posted | Number | mg | 48 - 52 months |
|
Adverse event data collected over 48 month peanut SLIT treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Peanut (Liquid Peanut Extract) SLIT | All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC. Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Edwin Kim, MD; Director UNC Food Allergy Initiative | University of North Carolina at Chapel Hill | 919-537-3193 | edwinkim@email.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 2, 2016 | Apr 10, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 13, 2016 | Apr 10, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D021183 | Peanut Hypersensitivity |
| D005512 | Food Hypersensitivity |
| ID | Term |
|---|---|
| D000074924 | Nut and Peanut Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to maintain at the same dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.
| 52 months |
| Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC | A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to decrease by one dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data. | 52 months |
With published concerns for the development of eosinophilic gastrointestinal disease after food immunotherapy, will report the number of participants with gastrointestinal and possible gastrointestinal eosinophilic adverse events during SLIT therapy |
| 48 months |
| Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (wheal size in mm during peanut skin prick test) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | 48 months |
| Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (serum levels of peanut specific IgE in kU/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | 48 months |
| Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (serum levels of peanut-specific IgG4 in mg/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | 48 months |
| Participants |
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| Age, Continuous | Inclusion criteria: age 1 year up to but not including 12 years. | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Peanut-specific IgE (kU/L) | Median | Full Range | kU/L |
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| Peanut skin prick test wheal size (mm) | Median | Full Range | mm |
|
|
|
| Primary | Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population | An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 10% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect. | Posted | Number | mg | 48-52 months |
|
|
|
| Primary | Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half. | A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to reduce by half, also called half-life of sensitivity threshold. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data. | Posted | Number | weeks | 52 months |
|
|
|
| Primary | Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC | A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to maintain at the same dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data. | Posted | Number | weeks | 52 months |
|
|
|
| Primary | Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC | A population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to decrease by one dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data. | Posted | Number | weeks | 52 months |
|
|
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| Secondary | Number of Participants With Adverse Events and Serious Adverse Events During the Study. | Number of participants with adverse events (AEs) and serious adverse events (SAEs) during the SLIT treatment portion of the study. | Posted | Count of Participants | Participants | 48 months |
|
|
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| Secondary | Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events. | With published concerns for the development of eosinophilic gastrointestinal disease after food immunotherapy, will report the number of participants with gastrointestinal and possible gastrointestinal eosinophilic adverse events during SLIT therapy | Posted | Count of Participants | Participants | 48 months |
|
|
|
| Secondary | Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (wheal size in mm during peanut skin prick test) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | Posted | Median | Full Range | mm | 48 months |
|
|
|
| Secondary | Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (serum levels of peanut specific IgE in kU/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | Posted | Median | Full Range | kU/L | 48 months |
|
|
|
| Secondary | Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed | Comparative estimates of changes in immune parameters (serum levels of peanut-specific IgG4 in mg/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC). | Posted | Median | Full Range | mg/L | 48 months |
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| 0 |
| 54 |
| 0 |
| 54 |
| 53 |
| 54 |
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Runny nose | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Oropharyngeal itch | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Coughing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Itchy nose | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin itch | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Lip swelling | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Eye swelling | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Eye itch | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Eye tearing | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hives | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Belly pain | Gastrointestinal disorders | Systematic Assessment |
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| Nasal congestion | Skin and subcutaneous tissue disorders | Systematic Assessment |
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