Walnut Oral Immunotherapy for Tree Nut Allergy-CHOP
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- effectiveness of walnut immunotherapy on desensitization to test tree nut or reduction in serum specific IgE
研究概览
简要总结
The purpose of this research study is to learn about the medical effects, safety, and how the Walnut Oral Immunotherapy (OIT) treatment affects your body (immune system). This type of immunotherapy involves giving increasing doses of walnut allergen to gradually build up a person's tolerance to walnut and at least one other tree nut. The goal of the study is to determine whether participants can tolerate (eat) walnuts and at least one other tree nut in their diet after stopping the study therapy.
详细描述
Our central hypothesis is that tree nut allergic subjects with multiple tree nut allergies will experience both clinical desensitization and immunologic evidence of a shift towards tolerance induction to multiple tree nuts when treated with OIT to walnut protein alone. We will address our hypothesis through investigations focused on the following objectives:
Objective #1: Examine the role of specific OIT to walnut protein in the induction of clinical desensitization to other tree nuts.
Objective #2: Determine the role of specific OIT to walnut protein in the induction of clinical desensitization to walnut.
Objective #3: Determine the change in tree nut specific immune parameters associated with OIT related to clinical desensitization and a shift towards oral tolerance.
Primary Objective:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 to 21 years, either sex, any race, any ethnicity with a convincing clinical history of walnut or another tree nut allergy and either a positive prick skin test (>3mm) or serologic evidence of allergic sensitization (defined as specific IgE>0.35 kU/L) to walnut and at least one other tree.
- •A positive <2000 mg protein oral food challenge at enrollment to walnut and to one other tree nut.
- •Written informed consent from participant and/or parent/guardian, including assent where indicated.
- •All females of child-bearing age must be using appropriate birth control or practicing abstinence.
排除标准
- •History of severe anaphylaxis to walnut or other tree nuts, defined as symptoms associated with hypoxia, hypotension or neurologic compromise (cyanosis or SpO2<92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence).
- •Known allergy to oat
- •Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy or other respiratory or medical conditions deemed by the investigator to put subject at increased risk of anaphylaxis or poor outcomes from receiving OIT or undergoing food challenge.
- •Poor control or persistent activation of atopic dermatitis
- •Active eosinophilic or other inflammatory (e.g., celiac) gastrointestinal disease in the past 2 years.
- •Participation in any interventional study for food allergy in the past 6 months
- •Participant is on "build-up phase" of immunotherapy (i.e., has not reached maintenance dosing).
- •Severe asthma (2007 NHLBI Criteria Steps 5 or 6, see Appendix 2)
- •Mild or moderate (2007 NHLBI Criteria Steps 1-4) asthma with any of the following criteria met:
- •FEV1 < 80% of predicted, or FEV1/FVC < 75%, with or without controller medications or
- •ICS dosing of > 500 mcg daily fluticasone (or equivalent inhaled corticosteroids based on NHLBI dosing chart) or
- •History of daily oral steroid dosing for > 1 month during the past year or
- •Burst of oral, IM, or IV steroids for >3 days in the past 6 months for asthma control or
- •> 1 burst of oral, IM or IV steroids in the past year for asthma control or
- •> 1 hospitalization in the past year for asthma or
- •> 1 ER visit in the past 6 months for asthma
- •Inability to discontinue antihistamines for initial day escalation, skin testing or OFC
- •Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator therapy (not including corticosteroids) or biologic therapy within the past year
- •Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
研究组 & 干预措施
walnut powder
Subjects will be randomized in a 2:1 ratio into either an active treatment group (final dose 1500 mg walnut protein, n=20) or a placebo group (n=10). Subjects will undergo a one-day desensitization protocol designed to enable the subject to tolerate 6 mg of walnut protein or placebo (initial day escalation phase). After the initial escalation day achieving at least 1.5 mg and up to 6 mg of walnut protein or placebo, dosing build-up will occur every two weeks through dose 24 at 34 weeks. A maintenance dose will be given for 4 weeks followed by a 5 gram protein OFC to walnut and a 5 gram protein OFC to a second tree nut (at ~38 weeks), after which the study will be unblinded.
干预措施: walnut powder (Drug)
placebo arm
Subjects will be randomized in a 2:1 ratio into either an active treatment group (final dose 1500 mg walnut protein, n=20) or a placebo group (n=10). Subjects will undergo a one-day desensitization protocol designed to enable the subject to tolerate 6 mg of walnut protein or placebo (initial day escalation phase). After the initial escalation day achieving at least 1.5 mg and up to 6 mg of walnut protein or placebo, dosing build-up will occur every two weeks through dose 24 at 34 weeks. A maintenance dose will be given for 4 weeks followed by a 5 gram protein OFC to walnut and a 5 gram protein OFC to a second tree nut (at ~38 weeks), after which the study will be unblinded. Placebo subjects that fail the OFC will be crossed over to active treatment and escalated as described to the 1500 mg target dose.
干预措施: walnut powder (Drug)
结局指标
主要结局
effectiveness of walnut immunotherapy on desensitization to test tree nut or reduction in serum specific IgE
时间窗: 38 weeks
The primary clinical efficacy outcome of the study will be the change from baseline OFC in cumulative dose reached at the desensitization OFC to the test tree nut.
次要结局
- The percentage of subjects who reach a cumulative dose of 5000 mg and 2000 mg at the desensitization OFC to walnut and to the test tree nut (desensitization OFC is at ~38 weeks)(38 weeks)
研究者
Jonathan Spergel
MD, PhD
Children's Hospital of Philadelphia