UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Prevention of egg allergy in infants with atopic dermatitis.
Title of the study (Brief title)	Prevention of egg allergy with tiny amount intake.
Region	Japan

Condition
Condition	food allergy
Classification by specialty	Clinical immunology Pediatrics Dermatology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate whether early introduction of food protein in complementary food at six months old can reduce onset of food allergy in infants with atopic dermatitis.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Negative diagnostic rate of food challenge test with hen's egg at one year old.
Key secondary outcomes	Measurement of the following bio markers of the subjects at their entry, nine months old and one year old: - antigen-specific antibody IgG1, IgG4, IgA and IgE in serum. - serum TARC. - antigen-specific antibody IgG1, IgG4, IgA and IgE in saliva.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is considered as a block.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Prevention
Type of intervention	Food
Interventions/Control_1	Subjects are fed with 50 mg of egg powder daily starting at six months old. After three months, amount of egg powder is increased to 250mg. During the intervention, subjects are not allowed to eat any other food that contains egg.
Interventions/Control_2	Subjects are fed with placebo (pumpkin) powder daily starting at six months old. During the intervention, subjects are not allowed to eat any other food that contains egg.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	4 months-old <=
Age-upper limit	6 months-old >
Gender	Male and Female
Key inclusion criteria	Infants aged four to five months old who were diagnosed with atopic dermatitis by a physician.
Key exclusion criteria	(1) Infants born before 37 weeks of gestation. (2) Infants who have already being fed with egg. (3) Infants with a history of immediate type allergic reaction to egg. (4) Infants with possible atypical food allergy other than immediate type food allergy. (5) Infants with severe complications.
Target sample size	200

Research contact person
Name of lead principal investigator	Yukihiro Ohya
Organization	National Center for Child Health and Development
Division name	Division of Allergy
Address	2-10-1 Okura Setagaya-ku Tokyo
TEL	0334160181
Email	ohya-y@ncchd.go.jp

Public contact
Name of contact person	Shigenori Kabashima, Osamu Natsume
Organization	National Center for Child Health and Development
Division name	Division of allergy
Address	2-10-1 Okura Setagaya-ku Tokyo
TEL	0334160181
Homepage URL
Email	natsume-o@ncchd.go.jp

Sponsor
Institute	National Center for Child Health and Development
Institute
Department

Funding Source
Organization	Ministry of Health, Labour and Welfare scientific research
Organization
Division
Category of Funding Organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	国立成育医療研究センター

Other administrative information
Date of disclosure of the study information	2012 Year 08 Month 10 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2012 Year 03 Month 30 Day
Anticipated trial start date	2012 Year 09 Month 01 Day
Last follow-up date	2015 Year 03 Month 30 Day
Date of closure to data entry	2015 Year 04 Month 18 Day
Date trial data considered complete	2015 Year 05 Month 15 Day
Date analysis concluded	2015 Year 07 Month 21 Day

Related information
URL releasing protocol	http://www.ncchd.go.jp/en/hospital/about/section/medical_subspecialties/pdf/PETITprotocol.pdf
Publication of results	Published
URL releasing results	http://www.sciencedirect.com/science/article/pii/S0140673616314180?via%3Dihub
Results	Lancet. 2017 Jan 21;389(10066):276-286. doi: 10.1016/S0140-6736(16)31418-0. Between Sept 18, 2012, and Feb 13, 2015, we randomly allocated 147 participants (73 [50%] to the egg group and 74 [50%] to the placebo group). This trial was terminated on the basis of the results of the scheduled interim analysis of 100 participants, which showed a significant difference between the two groups (four [9%] of 47 participants had an egg allergy in the egg group vs 18 [38%] of 47 in the placebo group; risk ratio 0.222 [95% CI 0.081-0.607]; p=0.0012). In the primary analysis population, five (8%) of 60 participants had an egg allergy in the egg group compared with 23 (38%) of 61 in the placebo group (risk ratio 0.221 [0.090-0.543]; p=0.0001). The only difference in adverse events between groups was admissions to hospital (six [10%] of 60 in the egg group vs none in the placebo group; p=0.022). 19 acute events occurred in nine (15%) participants in the egg group versus 14 events in 11 (18%) participants in the placebo group after intake of the trial powder. conclusion Introduction of heated egg in a stepwise manner along with aggressive eczema treatment is a safe and efficacious way to prevent egg allergy in high-risk infants. In this study, we developed a practical approach to overcome the second wave of the allergic epidemic caused by food allergy.
Other related information	We revised the registration at 26 June 2014, for revealing the timing of interventions and data samplings of secondary outcome from "start of the study, after 3 months, at the end" to "at their entry (4 to 6 months of age), nine months old and one year old". Also the method of randomization was revised at 26 June 2014 because it was incorrectly translated in Stratification and Blocking. The institution consideration was incorrect until 2015 July . So we revised it at 3rd August 2015.

Management information
Registered date	2012 Year 08 Month 10 Day
Last modified on	2017 Year 11 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000010190