Low Dose Multi-Nut Oral Immunotherapy in Pre-schoolers (LMNOP): a Pragmatic Randomised Controlled Trial of Low Dose Multi-Nut Oral Immunotherapy Versus Standard Care for the Treatment of Multi-Nut Allergies in Young Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Main Trial: Comparison of the number of participants who pass their OFC after the 18-month treatment phase for both study nuts between the Multi-Nut OIT Group and Standard Care Group
研究概览
简要总结
The LMNOP trial will be a 2-armed, open-label, randomised controlled trial (RCT), 2:1. Over a period of 18 months, children in the Multi-Nut Oral Immunotherapy Treatment (OIT) Group (experimental arm) will undergo low dose OIT to two nuts they are allergic to. At this time, children in the Standard Care Group (control arm) will be instructed to strictly avoid consuming two nuts they are allergic to. Avoiding consuming nut allergens is the standard care advice for children with peanut/tree nut allergies in Australia. The trial will assess the difference in the proportion of participants undergoing Multi-Nut OIT who can achieve sustained unresponsiveness (SU) compared to the proportion of participants avoiding nuts who develop natural tolerance (NT), i.e. grow out of their allergy. SU is when a participant can pass an oral food challenge (OFC) after having paused OIT treatment for several weeks. Participants will be between the ages of 18 and 36 months at the time of screening. The first 12 participants enrolled will be part of the pilot phase, with a total of n = 45 for the main trial.
It is hypothesised that there will be a higher proportion of participants in the Multi-Nut OIT Group versus the Standard Care Group who pass the OFC following the 18-month treatment phase. That is, a higher proportion of participants in the Multi-Nut OIT Group will achieve SU compared to participants in the Standard Care Group achieving NT.
详细描述
The LMNOP trial is a novel RCT assessing whether, over a period of 18 months, children undergoing low dose, multi-nut OIT can safely achieve SU at a higher rate than children under standard care who develop NT to peanut and tree nuts.
Trial Time Line
Study Entry - Children will undergo a screening skin prick test (SPT) to two of peanut, cashew, almond, hazelnut and/or walnut and OFC.
Children who meet the study eligibility criteria will be randomisation to either the Multi-Nut OIT Group or Standard Care Group for 18 months.
Multi-Nut OIT Group:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 36 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is between the ages of 18 and 36 months at the time of Screening visit 1
- •Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf
- •IgE-mediated allergy to 2 of peanut, almond, cashew, hazelnut or walnut, confirmed by:
- •Nut 1 pre-screening:
- •For at least one of almond, cashew, hazelnut or walnut (Nut 1)*:
- •History of ingestion with IgE-mediated reaction (birth to present) AND
- •History of SPT ≥3mm OR History of sIgE ≥0.35 number of kilounits per liter (KuL) AND
- •Nut 2 pre-screening:
- •For a second nut out of peanut, almond, cashew, hazelnut or walnut (Nut 2):
- •History of SPT ≥3mm OR History sIgE ≥0.35 KuL
- •In clinic screening: Participants meeting pre-screening criteria for Nuts 1 and 2 above will be invited for in-clinic screening
- •SPT: wheal size ≥3mm at Visit 1 for 2 of peanut, almond, cashew, hazelnut or walnut AND
- •OFC: react to ≤3000 mg protein top dose (4449 mg cumulative) in open, single nut OFC for 2 of peanut, almond, cashew, hazelnut or walnut
- •OFC not needed if:
- •History of failed OFC within past 3 months (confirmed by investigator review of discharge summary) OR History of anaphylaxis after ingestion within past 3 months based on investigator judgement +/- review of ER/Ambulance/medical notes
- •*Peanut is not included as Nut 1 to reduce the incidence of screening children with a peanut allergy only - children with peanut allergy may have been advised to avoid all other nuts. We require children to have eaten and reacted to at least one tree nut, and then the 2nd nut, which children may or may not have eaten, can be peanut or a tree nut.
排除标准
- •History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing more than 2 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
- •Severe anaphylaxis at study screening OFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring more than 2 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
- •Fails either screening OFC on dose 1 (0.5 mg).
- •Underlying medical conditions that increase the risks associated with anaphylaxis (e.g., cardiac disease or poorly controlled asthma (defined below))
- •Confirmed eosinophilic esophagitis (EoE) or history indicating EoE
- •Current use of beta-blockers or angiotensin-converting enzyme (ACE) inhibitors
- •Receiving systemic immunomodulatory treatment
- •Not commenced or unable to eat solid food
- •Weight <7.5kgs (recommended minimum weight for EpiPen Jr (adrenaline autoinjector))
- •Has a sibling in the study
- •Defining uncontrolled asthma (Global Initiative for Asthma. Asthma management and prevention for adults and children older than 5 years)
- •In the past 4 weeks, has the patient had:
- •Daytime symptoms more than twice/week? Any night waking due to asthma? Short Acting Beta Agonist (SABA) reliever needed more than twice/week? Any activity limitation due to asthma? Uncontrolled - answered yes to 3-4 of these
研究组 & 干预措施
Multi-nut OIT
Participants will have a personalised combination of two nuts they are allergic to for their multi-nut OIT (a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut). In the escalation visit, participants will receive 5 increasing doses of personalised multi-nut OIT in clinic at 20-minute intervals: 1 mg, 3 mg, 6 mg, 12 mg, 24 mg total nut protein, 12 mg/nut. The build-up phase will consist of daily home doses of multi-nut OIT and clinic visits every 2 weeks for up-dosing, up to a maintenance dose of 600 mg total protein, 300 mg/nut, over 3-8 months. In the maintenance phase, participants will continue to take their multi-nut OIT dose of 600 mg total protein each day at home for the remainder of the 18 months, with visits to the clinic every 3 months.
干预措施: Multi-nut OIT (Other)
Standard Care
Strict avoidance of the 2 study nuts the participants are allergic to over 18 months - a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut, as per standard care instructions for children with allergies in Australia.
结局指标
主要结局
Main Trial: Comparison of the number of participants who pass their OFC after the 18-month treatment phase for both study nuts between the Multi-Nut OIT Group and Standard Care Group
时间窗: At 18 months post commencement of treatment
In both groups, passing requires participants tolerating all OFC doses for both of their study nuts. For the Multi-Nut OIT Group, participants must pass their OFC at the end of the 18-month treatment phase, and then pass another OFC after 4 weeks of no OIT. For the Standard Care Group, participants must pass their OFC after the 18-month period. Participants have a personalised combination of two nuts: a. peanut, b. almond, c. cashew, d. hazelnut, e. walnut, as nominated at study screening.
次要结局
- Main Trial Ad Libitum Phase: Difference between the two groups in change in SPT wheal size from 18-months treatment phase assessment to the 12-month Ad libitum phase assessment(At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment)
- Main Trial: Difference between the two groups in change in levels of specific Immunoglobulin E (sIgE) at screening and at 18 months(Screening and at 18 months)
- Main Trial: Total number of missed doses overall (all participants) in the Multi-Nut OIT Group over the 18 month treatment phase(During the 18-month treatment phase)
- Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in quality of life scores for the parents using the ICEpop CAPability measure for Adults (ICECAP-A)(Screening and at 18 months)
- Main Trial: Difference between the two groups in change in SPT wheal size at screening and at 18 months(Screening and at 18 months)
- Main Trial Ad Libitum Phase: Comparison of the number of participants who pass their OFC after the 12 month Ad Libitum phase for both study nuts between the Multi-Nut OIT Group and Standard Care Group(At 32 months)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the frequency of study nut consumption during the Ad libitum phase(During the 12-month Ad libitum phase)
- Pilot Phase: Number of children at screening who refuse, are eligible, or are ineligible(At study screening, up to 4 weeks before starting treatment)
- Main Trial: Difference between the Multi-nut OIT Group in comparison to the Standard Care Group in the proportion and severity of reported adverse events (AE) related to study nut ingestion during the 18-month treatment phase(During the 18-month treatment phase)
- Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in quality of life scores for the children, measured by the Food Allergy Quality of Life-Parent Form (FAQL-PF)(Screening and at 18 months)
- Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the number of allergy-related healthcare visits from randomisation to 18 months(Randomisation to 18 months)
- Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from screening to 18 months in State/Trait anxiety using the State/Trait Anxiety Inventory (STAI)(Screening and at 18 months)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the proportion and severity of reported AEs related to study nut ingestion during the 12-month Ad libitum phase(During the 12 month Ad libitum phase)
- Main Trial: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from the start to the end of the Ad libitum phase in quality of life scores for the children, measured by the FAQL-PF(At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment)
- Main Trial Ad Libitum Phase: Difference between the two groups in change levels of BAT from 18-months treatment phase assessment to the 12-month Ad libitum phase assessment(At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment)
- Pilot Phase: Number and severity of AEs during the screening OFC for all participants(At study screening, up to 4 weeks before starting treatment)
- Main Trial: Difference between the two groups in change in levels of component-resolved diagnostic (CRD) at screening and at 18 months(Screening and at 18 months)
- Main Trial: Difference between the two groups in change in levels of basophil activation test (BAT) at screening and at 18 months(Screening and at 18 months)
- Main Trial: Mean number of missed daily doses per participant in the Multi-Nut OIT Group over the 18 month treatment phase(During the 18-month treatment phase)
- Main Trial: Difference between the two groups in change in levels of specific Immunoglobulin G4 (sIgG4) at screening and at 18 months(Screening and at 18 months)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the number of allergy-related healthcare visits during the 12-month Ad libitum phase(During the 12-month Ad libitum phase)
- Main Trial Ad Libitum Phase: Difference between the two groups in change in levels of sIgE from 18-months treatment phase assessment to the 12-month Ad libitum phase assessment(At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in the amount of study nut consumption during the Ad libitum phase(During the 12-month Ad libitum phase)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from the start to the end of the Ad libitum phase in quality of life scores for the parents using the ICECAP-A(At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment)
- Main Trial Ad Libitum Phase: Difference between the Multi-Nut OIT Group in comparison to the Standard Care Group in mean change from the start to the end of the Ad libitum phase in State/Trait anxiety using the STAI(At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment)
- Main Trial Ad Libitum Phase: Difference between the two groups in change in levels of sIgG4 from 18-months treatment phase assessment to the 12-month Ad libitum phase assessment(At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment)
- Main Trial Ad Libitum Phase: Difference between the two groups in change levels of CRD from 18-months treatment phase assessment to the 12-month Ad libitum phase assessment(At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment)
- Pilot Phase: Number of participants in the Multi-Nut OIT Group who complete escalation(At completion of first day of treatment)
- Pilot Phase: Number and severity of AEs for the Multi-Nut OIT Group during escalation(At completion of first day of treatment)
- Pilot Phase: Total number of missed doses overall (all participants) in the Multi-Nut OIT Group over the build-up phase(During the build-up phase, between 3-8 month period after commencing treatment)
- Pilot Phase: Mean number of missed daily doses per participant in the Multi-Nut OIT Group over the build-up phase(During the build-up phase, between 3-8 month period after commencing treatment)
- Pilot Phase: Number of children at recruitment who agree or refuse to participate(At study recruitment, up to 4 weeks before starting treatment)
- Pilot Phase: Number of participants in the Multi-Nut OIT Group who complete the build-up phase(At completion of build-up, between 3-8 months after commencing treatment)
- Pilot Phase: Number and severity of AEs for the Multi-Nut OIT Group during the build-up phase(During the build-up phase, between 3-8 month period after commencing treatment)
- Pilot Phase: Number of participants in the Multi-Nut OIT Group and the Standard Care Group who withdraw, discontinue, and/or experience 1 or more protocol violations(During the 18 month treatment phase)