UMIN-CTR Clinical Trial

Public title

Safety of small-dose introduction and stepwise increases for induction of tolerance in children with hen's egg allergy: a single center randomized double-blind parallel-group phase II trial

Acronym

Safety of small-dose introduction and stepwise increases in children with hen's egg allergy (STITCH): a randomized double-blind parallel-group trial

Scientific Title

Safety of small-dose introduction and stepwise increases for tolerance induction in children with hen's egg allergy: a single center randomized double-blind parallel-group phase II trial

Scientific Title:Acronym

A randomized trial to investigate safety of small-dose introduction for children with hen's egg allergy (STITCH)

Region

Japan

Condition

Food allergy

Classification by specialty

Clinical immunology	Pediatrics	Child

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate whether very small amount of starting method is safer than fixed-quantity maintenance method by randomized double-blind parallel-group trial on hen's egg introduction

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Time to onset of IgE-dependent immediate reaction after starting the experimental diet

Key secondary outcomes

1.Secondary outcomes on effectiveness:
(1) Change in cumulative tolerated dose on formal registration day to at 24 and 48 weeks after starting the experimental diet
(2) Whether the oral challenge test of hen's egg is negative at 48 weeks after starting the experimental diet
(3) Change in total IgE value on temporary registration day to that at 48 weeks after starting the experimental diet
(4) Change in egg white- and ovomucoid-specific IgE value on temporary registration day to that at 24 and 48 weeks after starting the experimental diet
(5) Change in egg white- and ovomucoid-specific IgG4 value on temporary registration day to that at 24 and 48 weeks after starting the experimental diet
(6) Change in urinary PGDM (tetranor-PGDM, tetranor-PGEM) value 4 h after the intake of experimental diet on the starting day and at 4, 12, 24, 36, and 48 weeks
(7) Ratio of urinary PGDM (tetranor-PGDM, tetranor-PGEM) value before and 4 h after the intake of experimental diet on the starting day and at 4, 12, 24, 36, and 48 weeks
(8) Change in difference of urinary PGDM (tetranor-PGDM, tetranor-PGEM) value between before and 4 h after the intake of experimental diet on the starting day and at 4, 12, 24, 36, and 48 weeks
2.Secondary outcomes on safety:
(1) Time to onset of IgE-dependent reaction after starting the experimental diet
(2) The maximum severity score of IgE-dependent allergic reaction against hen's egg caused by experimental diet
(3) Number of symptom days related to IgE-dependent allergic reaction against hen's egg
(4) Presence or absence of anaphylaxis related to the experimental diet
(5) Presence or absence of emergency room visits related to the experimental diet
(6) Number and proportion of participants who experienced severe adverse reactions at least once
(7) Number of participants who experienced severe adverse reactions, reaction appearance rate, and number of reactions
(Continued in "Other related information")

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Food

Interventions/Control_1

1.Very small amount at the starting method (The experimental therapy group)
-We set a cumulative tolerated dose of the hen's egg intake by oral challenge test on formal registration day.
-Patients take in the experimental diet including the hen's egg (egg white and yolk) of 1/50 quantity of the cumulative tolerated dose the day after the initiation for 4 weeks.
-Patients take in the experimental diet including the hen's egg of 1/10 quantity of the cumulative tolerated dose the day after from 4 to 8 weeks.
-Patients take in the experimental diet including the hen's egg of half quantity of the cumulative tolerated dose the day after from 8 to 12 weeks.
-Patients take in the experimental diet including the hen's egg of a cumulative tolerated dose the day after from 12 to 48 weeks.

Interventions/Control_2

2.Fixed-quantity maintenance method (Standard therapy group)
-We set a cumulative tolerated dose of the hen's egg intake by oral challenge test on formal registration day.
-Patients take in the experimental diet including the hen's egg of a cumulative tolerated dose every day until 48 weeks later.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

1

years-old

<=

Age-upper limit

18

years-old

>=

Gender

Male and Female

Key inclusion criteria

Inclusion criteria for temporary registration:
(1)Patients diagnosed with hen's egg allergy or suspected of hen's egg allergy (egg white-specific IgE >= 0.35 kUA/L) by a medical doctor from up to 1 year before the temporary registration date
(2)Aged 1-18 years
(3)Informed written consent from patients or authorized guardians (patients aged >= 16 years gave their own written consent)

Inclusion criteria for formal registration:
(1)Patients temporarily registered who fulfill the inclusion criteria and do not conflict with the exclusion criteria for temporary registration, including the formal registration day
(2)Patients diagnosed with hen's egg allergy by an oral challenge test with 10 g of a hen's egg (egg white and yolk) within 90 days after temporary registration
(3)Patients with a cumulative tolerated dose of hen's egg determined by an oral challenge test with 10 g of a hen's egg (egg white and yolk)

Key exclusion criteria

Exclusion criteria for temporary registration:
(1)Patients born before 37 weeks of gestation
(2)Patients with siblings already enrolled
(3)Immunosuppressant or systemic steroid administration
(4)Patients planning to relocate or having difficulty making regular visits to our facility
(5)Patients with severe complications
(6)Allergy to rice, pumpkin, sugar beet, palm oil, cornstarch, baking powder, sweet potato, or trehalose
(7)Patients considered unsuitable for the study by the lead researcher or co-researchers for other reasons

Target sample size

80

Name of lead principal investigator

1st name	Fumi
Middle name
Last name	Ishikawa

Organization

National Center for Child Health and Development

Division name

Allergy Center

Zip code

157-8535

Address

2-10-1,Okura,Setagayaku,Tokyo 157-8535,Japan

TEL

0334160181

Email

allergy_research@ncchd.go.jp

Name of contact person

1st name	Kiwako
Middle name
Last name	Yamamoto-Hanada

Organization

National Center for Child Health and Development

Division name

Allergy Center

Zip code

157-8535

Address

2-10-1,Okura,Setagayaku,Tokyo 157-8535,Japan

TEL

0334160181

Homepage URL

Email

allergy_research@ncchd.go.jp

Institute

National Center for Child Health and Development

Institute

Department

Personal name

Organization

National Center for Child Health and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

IRB of National Center for Child Health and Development

Address

2-10-1,Okura,Setagayaku,Tokyo 157-8535,Japan

Tel

0334160181

Email

rinri@ncchd.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2021

Year

02

Month

24

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Terminated

Date of protocol fixation

2021

Year

02

Month

01

Day

Date of IRB

2021

Year

02

Month

01

Day

Anticipated trial start date

2021

Year

03

Month

01

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

(Continuation of "Key secondary outcomes")
3. Secondary outcomes on adherence and others:
(1) Days of experimental diet intake from starting day to 48 weeks after
(2) Whether good adherence or not after 48 weeks of starting the experimental diet
(3) VAS scale in the participant's resistance against experimental diet on starting day and at 4, 12, 24, 36, and 48 weeks
(4) FAQLQ score on the experimental diet on starting day and at 4, 12, 24, 36, and 48 weeks
(5) Atopic dermatitis severity score (EASI) on the starting day and at 4, 12, 24, 36, and 48 weeks
(6) Number of episodes of asthmatic exacerbation during the trial
(7) Presence or absence of non-IgE-mediated gastrointestinal allergy during the trial

Registered date

2021

Year

02

Month

17

Day

Last modified on

2022

Year

04

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049497