Challenging to Food With Escalating Thresholds for Reducing Food Allergy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Percentage of Children That Tolerate the Full Challenge
研究概览
简要总结
The primary objective of this study is to determine whether allowing ingestion of sub-threshold amounts of peanut in those with a high threshold (tolerate at least 143 mg peanut protein on supervised double-blind, placebo-controlled oral food challenge [DBPCFC]) will be associated with attaining even higher thresholds over time in children with high threshold peanut allergy compared to those avoiding peanut. The secondary clinical objectives include assessing the development of sustained unresponsiveness (SU, a surrogate term for tolerance without daily ingestion), effects on quality of life, and safety compared to those avoiding peanut. Additionally, this study will phenotype the allergic response to peanut based on threshold and response to exposure. Mechanistic study objectives will determine the immune and molecular basis of the high threshold endotype, identify predictors of response to exposure, and determine mechanisms and biomarkers of remission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Although a double-blind, placebo controlled oral food challenge test is used in screening to identify participants eligible to continue to randomization in the study, those randomized to peanut ingestion versus avoidance have participants aware and unmasked regarding the study arm to which they were randomized
入排标准
- 年龄范围
- 4 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject and/or parent guardian must be able to understand and provide informed consent.
- •Inclusion criteria for screening DBPCFC:
- •Age 4-14 years
- •either sex
- •any race, any ethnicity
- •who are enrolled while strictly avoiding peanut
- •have a history of sensitization (detectable peanut IgE >0.35 kUA/L)
- •Inclusion criteria for randomization:
- •On screening DBPCFC are able to ingest >= 143 mg peanut protein but < 5043 mg peanut protein.
- •All children will have documented consent and assent as is appropriate for age.
排除标准
- •Individuals who meet any of these criteria are not eligible for enrollment as study participants:
- •Inability or unwillingness of a participant to give written informed consent or comply with study protocol
- •Serum peanut-specific IgE antibody level > 50 kUA/L
- •Recent (within the past 2 years) life-threatening (grade 3) anaphylactic reaction to peanut.
- •Any disorder in which epinephrine is contraindicated such as known hypertension or cardia rhythm disorders.
- •History of chronic disease requiring therapy (other than asthma, atopic dermatitis, rhinitis).
- •On a build-up phase of any allergen immunotherapy.
- •For those with a history of asthma, the following are assessed and any of the following is an exclusion (markers of current uncontrolled or moderate to severe asthma):
- •FEV1 value <80% predicted (only for participants age 7 years or older and are able to perform spirometry)
- •ACT or cACT < 20
- •>Step 3 controller therapy as defined for children 0-4, 5-11 and >=12 years of age by EPR-3 tables
- •Use of steroid medications in the following manners:
- •history of daily oral steroid dosing for >1 month during the past year,
- •having 1 burst or steroid course within the past 6 months, or
- •having >1 burst oral steroid course within the past 12 months.
- •Asthma requiring >1 hospitalization in the past year for asthma or >1 ED visit in the past 6 months for asthma, or any prior intubation/mechanical ventilation for asthma/wheezing.
- •When COVID related institutional restrictions on spirometry are in effect, spirometry will not be performed and peak flow will be used with 80% predicted as cut-off.
- •Gastrointestinal eosinophilic disorders, esophagitis, gastroenteritis.
- •Use of short-acting antihistamines (diphenhydramine, etc.) more than one time within 3 days prior to DBPCFC or skin testing.*
- •Use of medium-acting antihistamines (hydroxyzine, loratadine, etc.) more than one time within 7 days of DBPCFC or skin testing.*
- •Use of systemic steroid medications (IV, IM or oral) for indications other than asthma for > 3 weeks within the past 6 months
- •Use of beta-blockers (oral), (ACE) inhibitors, angiotensin-receptor blockers or calcium channel blockers.
- •Participation in any trials of therapeutic interventions for food allergy in the past year.
- •Therapy with anti-IgE or other biologics, including within 1 year of enrollment.
- •Use of investigational drugs within 52 weeks of participation.
- •Allergy to all of the following: oat, rice, corn, tapioca.
- •Pregnancy
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
- •*Any subject meeting these criteria during the visits can be rescheduled for the oral food challenge or prick skin testing.*
研究组 & 干预措施
Treatment
Ingests peanut - . Depending upon reaction threshold, participants may begin with different starting amounts of store bought peanut butter measured with study-supplied kitchen measuring spoons.
干预措施: Peanut Protein (Biological)
Avoidance
Avoids peanut, standard care
干预措施: Continued peanut avoidance (Other)
结局指标
主要结局
Percentage of Children That Tolerate the Full Challenge
时间窗: 72 weeks
The difference between the treatment and comparison (avoidance) groups in the percentage of children who by the endpoint double-blind, placebo-controlled oral food challenge (DBPCFC) tolerate a dose at least 2 steps higher than their baseline DBPCFC or 9043 mg of peanut protein. Due to missing data in the primary endpoint, the protocol \& SAP specified a priori that missing data would be imputed using multiple imputation and results based on 30 completed-imputed data sets would be combined using Rubin's rule. In the Peanut Protein group, the observed data was so strong that participants with missing data were also imputed as success across all imputations (hence, 100% success rate). In the Peanut Avoidance group, there was more variability in the proportion of successes across imputations and these varying proportions were averaged. Missing data were imputed and results were pooled.
次要结局
- The Percentage of Children That Achieve Sustained Unresponsiveness(96 weeks)
- Number of Children With Acute Allergic Reactions(96 weeks)
- Mean Change in Food Allergy Quality of Life Parental Burden Instrument(baseline and at 72 weeks)
- Mean Change in SPT Wheal Size(Baseline and 72 weeks)
- Mean Change in Peanut-specific IgE(Baseline and 72 weeks)
- Mean Change in Peanut-specific IgG4(Baseline and 72 weeks)
研究者
Scott Sicherer
Professor
Icahn School of Medicine at Mount Sinai