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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05049512




Registration number
NCT05049512
Ethics application status
Date submitted
8/09/2021
Date registered
20/09/2021

Titles & IDs
Public title
Low Dose Multi-Nut Oral Immunotherapy in Pre-schoolers With a Multi-Nut Allergy
Scientific title
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
Secondary ID [1] 0 0
74540
Universal Trial Number (UTN)
Trial acronym
LMNOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergy, Nut 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Multi-nut OIT

Experimental: 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.

No intervention: 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.


Other interventions: Multi-nut OIT
Finely ground pure peanut, almond, cashew, hazelnut, and walnut.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
At 18 months post commencement of treatment
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
During the 18-month treatment phase
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Screening and at 18 months
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
Screening and at 18 months
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Screening and at 18 months
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Randomisation to 18 months
Secondary outcome [6] 0 0
Main Trial: Difference between the two groups in change in SPT wheal size at screening and at 18 months
Timepoint [6] 0 0
Screening and at 18 months
Secondary outcome [7] 0 0
Main Trial: Difference between the two groups in change in levels of specific Immunoglobulin E (sIgE) at screening and at 18 months
Timepoint [7] 0 0
Screening and at 18 months
Secondary outcome [8] 0 0
Main Trial: Difference between the two groups in change in levels of specific Immunoglobulin G4 (sIgG4) at screening and at 18 months
Timepoint [8] 0 0
Screening and at 18 months
Secondary outcome [9] 0 0
Main Trial: Difference between the two groups in change in levels of component-resolved diagnostic (CRD) at screening and at 18 months
Timepoint [9] 0 0
Screening and at 18 months
Secondary outcome [10] 0 0
Main Trial: Difference between the two groups in change in levels of basophil activation test (BAT) at screening and at 18 months
Timepoint [10] 0 0
Screening and at 18 months
Secondary outcome [11] 0 0
Main Trial: Total number of missed doses overall (all participants) in the Multi-Nut OIT Group over the 18 month treatment phase
Timepoint [11] 0 0
During the 18-month treatment phase
Secondary outcome [12] 0 0
Main Trial: Mean number of missed daily doses per participant in the Multi-Nut OIT Group over the 18 month treatment phase
Timepoint [12] 0 0
During the 18-month treatment phase
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
At 32 months
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
During the 12 month Ad libitum phase
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment
Secondary outcome [17] 0 0
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
Timepoint [17] 0 0
At the 18-month treatment phase assessment and at the 12 month Ad libitum phase assessment
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
During the 12-month Ad libitum phase
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment
Secondary outcome [22] 0 0
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
Timepoint [22] 0 0
At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment
Secondary outcome [23] 0 0
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
Timepoint [23] 0 0
At the 18-month treatment phase assessment and at the 12-month Ad libitum phase assessment
Secondary outcome [24] 0 0
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
Timepoint [24] 0 0
During the 12-month Ad libitum phase
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
During the 12-month Ad libitum phase
Secondary outcome [26] 0 0
Pilot Phase: Number of children at screening who refuse, are eligible, or are ineligible
Timepoint [26] 0 0
At study screening, up to 4 weeks before starting treatment
Secondary outcome [27] 0 0
Pilot Phase: Number of children at recruitment who agree or refuse to participate
Timepoint [27] 0 0
At study recruitment, up to 4 weeks before starting treatment
Secondary outcome [28] 0 0
Pilot Phase: Number of participants in the Multi-Nut OIT Group who complete escalation
Timepoint [28] 0 0
At completion of first day of treatment
Secondary outcome [29] 0 0
Pilot Phase: Number of participants in the Multi-Nut OIT Group who complete the build-up phase
Timepoint [29] 0 0
At completion of build-up, between 3-8 months after commencing treatment
Secondary outcome [30] 0 0
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
Timepoint [30] 0 0
During the 18 month treatment phase
Secondary outcome [31] 0 0
Pilot Phase: Number and severity of AEs during the screening OFC for all participants
Timepoint [31] 0 0
At study screening, up to 4 weeks before starting treatment
Secondary outcome [32] 0 0
Pilot Phase: Number and severity of AEs for the Multi-Nut OIT Group during escalation
Timepoint [32] 0 0
At completion of first day of treatment
Secondary outcome [33] 0 0
Pilot Phase: Number and severity of AEs for the Multi-Nut OIT Group during the build-up phase
Timepoint [33] 0 0
During the build-up phase, between 3-8 month period after commencing treatment
Secondary outcome [34] 0 0
Pilot Phase: Total number of missed doses overall (all participants) in the Multi-Nut OIT Group over the build-up phase
Timepoint [34] 0 0
During the build-up phase, between 3-8 month period after commencing treatment
Secondary outcome [35] 0 0
Pilot Phase: Mean number of missed daily doses per participant in the Multi-Nut OIT Group over the build-up phase
Timepoint [35] 0 0
During the build-up phase, between 3-8 month period after commencing treatment

Eligibility
Key inclusion criteria
* 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)*:

1. History of ingestion with IgE-mediated reaction (birth to present) AND
2. 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

1. SPT: wheal size =3mm at Visit 1 for 2 of peanut, almond, cashew, hazelnut or walnut AND
2. 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.
Minimum age
18 Months
Maximum age
36 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kirsten Perrett, MBBS FRACP
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kirsten Perrett, MBBS FRACP
Address 0 0
Country 0 0
Phone 0 0
039936
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The de-identified data set that will be collected for this analysis of the LMNOP trial will be available six months after publication of the primary outcome. The study protocol may be obtained from the Murdoch Children's Research Institute. Prior to releasing any data, the following are required: a data access agreement must be signed between relevant parties; the LMNOP trial investigators must see and approve the analysis plan describing how the data will be analysed; there must be an agreement around appropriate acknowledgment; and any additional costs involved must be covered.

Should the study investigators be unavailable, this role is delegated to the Murdoch Children's Research Institute. Data will only be shared with a recognised research institute, which has approved the proposed analysis plan.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
Six months after the publication of the primary outcome
Available to whom?
Prior to releasing any data, the following are required: a data access agreement must be signed between relevant parties; the LMNOP trial investigators must see and approve the analysis plan describing how the data will be analysed; there must be an agreement around appropriate acknowledgment; and any additional costs involved must be covered.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.