Clinical Desensitization and Tolerance Following Peanut Oral Immunotherapy and Subsequent Allergen Avoidance
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Tolerance, Partial Tolerance, or Treatment Failure
研究概览
简要总结
The unifying objective of this project is to determine whether peanut oral immunotherapy (PN OIT) induced clinical tolerance in the context of food allergy is significantly associated with the expansion of a specific regulatory T cell subset (CD45RA- CD25++ FoxP3++) that is thought to be inducible in the gut-associated lymphoid compartment and associated with immunological tolerance.
The hypothesis of the study is that the induction of Treg cells will be associated with clinical tolerance.
The investigators will measure the change from baseline of induced Treg cells as a frequency of total CD4 T cells during active treatment and compare that between participants who achieve significant clinical tolerance (Tolerance and Partial Tolerance Groups as defined below) and those who do not (Treatment Failure Group).
详细描述
Clinical Objectives:
- To evaluate whether PN OIT induces increased tolerance, defined as a statistically significant increase in the median eliciting dose (ED) from a double-blind placebo-controlled food challenge (DBPCFC) before and after treatment with PN OIT and after subsequent allergen avoidance.
- To evaluate whether PN OIT induces clinical desensitization, defined as 1) a median 10-fold or greater increase in ED at DBPCFC before and after PN OIT treatment period 2) a statistically significant higher median ED at DBPCFC following treatment period between active and control treatment; and 3) a significantly lower frequency of accidental ingestion reactions in active versus control treatment.
- To evaluate the safety of PN OIT.
Mechanistic Objectives:
- To determine whether PN OIT induces a statistically significant increase in the TCR clonal diversity of Treg populations during active treatment among participants who achieve increased clinical tolerance (Tolerance and Partial Tolerance Groups as defined in clinical endpoints) versus the Treatment Failure Group.
- To determine whether PN OIT suppresses mast cells by inducing a significant suppression of the median ED on end-point dilution skin testing in actively treated participants by the end of maintenance therapy.
- To determine whether PN OIT suppresses basophils as defined by a 10-fold suppression of peanut-specific basophil ED in actively treated participants by end of a maintenance period.
- To determine whether either mast cell or basophil suppression at the end of maintenance therapy is significantly associated with clinical outcomes following avoidance.
Exploratory Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 7 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of peanut allergy by a positive skin prick test to peanut (reaction wheal at least 5 mm larger than saline control) and by medical history or Serum peanut-specific IgE >5 kU/L at screening visit.
- •Ara h 2 specific IgE >0.35 kU/L at screening visit
- •Ability to provide informed consent.
- •Males and females of all ethnic/racial groups aged 7-55 years old who are otherwise healthy.
- •React to less than 443 mg of peanut protein during DBPCFC1
排除标准
- •History of severe anaphylaxis as defined by hypoxia (cyanosis or SpO2 <92% during reaction), documented hypotension (documented systolic BP >30% below predicted normal for sex, height, weight or from known baseline), neurological compromise (confusion, loss of consciousness), or incontinence.
- •Severe or Moderate asthma as defined using the severity criteria of the current NHBLI Guidelines for the Diagnosis and Management of Asthma (http://www.nhlbi.nih.gov/guidelines/asthma/).
- •Poorly-controlled asthma as defined by FEV1 <80% or any of the following symptoms: nighttime awakening >2 days/week or rescue medication use >2 days / week.
- •Diagnosis of other severe or complicating medical problems, including autoimmune or chronic immune inflammatory conditions or gastrointestinal inflammatory conditions, including Celiac Disease, Inflammatory Bowel Disease and Eosinophilic Gastrointestinal Disorders
- •Inability to cooperate with and/or perform oral food challenge procedures.
- •Primary Immune Deficiency
- •Allergy to oat confirmed by skin prick testing and history
- •Current use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors
- •Women of childbearing potential who are pregnant, planning to become pregnant, or breastfeeding
- •Hemoglobin level less than 12.5 gm/dL at screening. Weight <23 kg
- •Use within the past 6 months of other systemic immunomodulatory treatments including allergen immunotherapy, or use of biologics with an immune target, including omalizumab.
- •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 may also exclude a participant from the study.
研究组 & 干预措施
Peanut Flour
Oral Immunotherapy with peanut flour.
干预措施: Peanut Flour (Drug)
Oat Flour
Oral Immunotherapy with oat flour.
干预措施: Oat Flour (Drug)
结局指标
主要结局
Tolerance, Partial Tolerance, or Treatment Failure
时间窗: Average 515 days from DBPCFC1 to DBPCFC3
1. Tolerance: Ingestion of 4430 mg of peanut protein at DBPCFC3 without symptoms. 2. Partial Tolerance: ED at DBPCFC3 \<4430 mg but =\>430 mg AND \>10-fold more than at DBPCFC1. 3. Treatment Failure - non desensitized: Failure to achieve the minimum maintenance dose (600 mg) of peanut protein by 12 months, or an ED \<1443 mg at DBPCFC2, or ED at DBPCFC3 \<443 mg OR \<10-fold more than at DBPCFC1. 4. Treatment Failure - withdrawal
次要结局
- Clinical: Tolerance(630 days)
- Clinical: Desensitization(518 days)
- Mechanistic: Change Eliciting Dose of End-point Dilution.(518 days)
- Mechanistic: Significant Gene Expression Changes by Transcriptional Profiling of Regulatory and Effector T Cell Populations(630 days)
- Clinical: Safety(630 days)
- Mechanistic: Change in Peanut Allergen-specific IgG4(518 days)
- Mechanistic: TCR Clonal Diversity(630 days)
- Mechanistic: Change in Basophil Eliciting Dose.(630 days)
研究者
Wayne G. Shreffler, MD, PhD
Principal Investigator
Massachusetts General Hospital