The EAT-On Study: Sensitisation, Allergy and Child Health

Obesity, Childhood Clinical Trial

Official title:

Effects of Early Introduction of Allergenic Foods Followed by Ad-libitum Consumption, on Food Allergic Sensitisation, Allergy and Measures of Child Health at 8 Years of Age in Exclusively Breastfed Infants

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03495583
• Other study ID #: GN2551
• Status: Enrolling by invitation
• Phase: N/A
• First received: April 4, 2018
• Last updated: April 4, 2018
• Start date: April 3, 2018
• Est. completion date: April 2021

Study information

• Verified date: March 2018
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The EAT Study showed a reduction in both sensitisation (to all foods) and clinical food allergy (to peanut and egg) among children who consumed allergenic food early compared with those who followed standard government feeding advice to exclusively consume breast milk for the first 6 months of life. The EAT-On Study aims to establish whether the effects seen at 3 years in the EAT study represent a delay in FA onset or sustained tolerance. EAT-On will also investigate the natural history (emergence and resolution) of FA in childhood; thus shaping dietary and management plans for allergic patients. Findings will inform future research and weaning recommendations for preventing FA.

Description:

Sensitisation/Allergy:

Food allergy (FA) is common, increasing in prevalence and represents a public health concern in many countries. FA increasingly affects geographic regions where rates of FA were previously low.(1-5) Data from the Enquiring About Tolerance (EAT) study, which enrolled 1303 exclusively breastfed three month old babies from the general population, showed that 8% of children had proven immediate-onset FA at three years of age. This equates to almost 1 in 10 children. (1) The early-introduction of specific food allergen(s) to infant diets is a successful strategy for the prevention of FA. Introduction of peanut to the infant diet before 11 months of age, protected against the development of peanut allergy in a high-risk, atopic population.(6) This effect persisted despite cessation of peanut consumption for 12 months.(7) In the EAT Study, children from the general population were randomised either to consume six commonly allergenic foods (cow's milk, egg, peanut, wheat, fish and sesame) from four months of age (early introduction group (EIG)), or to follow Department of Health (DoH) advice to exclusively breastfeed until about 6 months of age (standard introduction group (SIG)). The per-protocol analysis revealed a reduction in any FA of 7.3% versus 2.4% (p=0.01), for peanut allergy of 2.5% versus 0% (p=0.003) and for egg allergy 5.5% versus 1.4% (p=0.009) in the SIG and EIG respectively. (8) In the EAT study, between 1 and 3 years an intention-to-treat analysis (ITT) of sensitisation to individual foods showed a significant cumulative treatment effect of 35% (p=0.0095) in the EIG (unpublished data). Furthermore, in the per-protocol analyses (PP), we showed a statistically significant reduction of 41.6% (p=0.01) in skin prick test (SPT) sensitivity to any food at 1 year, and again at 3 years with a 67.3% relative reduction (RR) (p=0.002) in the EIG. These findings were particularly significant for individual food; at 3 years there was a relative reduction in skin-prick sensitivity to all individual foods and particularly for peanut (RR 67.1% p=0.007).

FA is a dynamic condition with egg and milk allergy typically developing in infancy and being outgrown and peanut and sesame allergy usually developing between the ages of 3-6 and persisting into adulthood. Whilst early introduction of commonly allergenic foods is effective in preventing food allergy in early childhood and within the confines of a randomised controlled trial (RCT), the longevity of this novel approach has not been tested and little is known about whether these effects are sustained after 'real world' ad libitum consumption. The EAT-On Study aims to investigate this by following-up children who were previously enrolled in the EAT Study when they are 8 years of age and investigating the natural history of food allergy, and how the intervention that was applied when children were 4-6 months of age influences food allergic sensitisation and clinical food allergy when they are 8 years of age.

Child Health:

Whilst the UK Department of Health recommends exclusive breastfeeding (EBF) until around six months of age, surveys suggest this is achieved by only 1% of mothers(9). Given the lack of EBF till 6 months of age, the majority of infants will require additional nutrition provided from formula and/or solid weaning foods. Indeed, 75% of infants have been introduced to solid food by 5 months of age (9). The nutritional consequences of different weaning regimens may have important consequences on obesity outcomes, but rigorous trials in this area are difficult to undertake, not least because of the necessary ethical concerns that pertain to the comparison of breast-feeding with alternate or complementary feeding strategies. The EAT cohort presents a unique opportunity to study this question further as the diet consumed by children who participated in the EIG of the EAT study is much higher in protein than breastmilk alone. Good quality studies have found that consumption of high protein formula milk in early infancy increases the risk of overweight in later childhood compared with breastfeeding, but the effect of high protein solid food consumption alongside breastfeeding in early infancy has not been studied. The majority of infants have solid food introduced before 6 months of age, and updated guidance advocates the introduction of a high protein food (peanut) from 'around 6 months of age' (UK(10) and Australia(11)), or at 4 months of age (USA(12)) to prevent a new onset of peanut allergy. It is therefore timely to explore how early diet, particularly with respect to high protein weaning diet, influences childhood obesity. This will lead to the development of clearer guidance in respect to early weaning diet which extends to other high protein foods, while taking in to account the risk of childhood obesity.

The nature of the EAT cohort means that between 4 and 6 months of age children were randomised either to a lower protein diet (SIG) or to a higher protein diet (EIG): breastmilk contains approximately 6% energy from protein whilst the EIG were asked to consume a diet containing at least 15% energy from protein, more than double that of the SIG. This cohort therefore offers a unique opportunity to explore the effect of differing energy consumption from dietary protein on overweight/obesity and markers of cardiovascular health in later childhood.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1235
• Est. completion date: April 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 8 Years

Eligibility

Inclusion Criteria:

• Previous participation in the EAT study

• Age 8 years +/- 12 months

Exclusion Criteria:

Related Conditions & MeSH terms

• Food Allergen Sensitisation
• Food Allergy in Children
• Food Hypersensitivity
• Hypersensitivity
• Obesity, Childhood
• Pediatric Obesity

Intervention

Other:
• Early introduction
Consumption of 2g/week of cow's milk, hen's egg, wheat, peanut, sesame and fish protein from 3 months of age (alongside breastfeeding)

Locations

Country	Name	City	State
United Kingdom	Paediatric Allergy	London

Sponsors (2)

Lead Sponsor	Collaborator
King's College London	Action Medical Research

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Allergic sensitisation	Between group differences in total number of cumulative sensitisations to the six study food allergens at age 8	3 years
Primary	Food allergy	Between group differences in cumulative food allergy (challenge confirmed) t the six study foods at age 8	3 years
Primary	Child Health	Between group differences in proportion of children who classified as overweight or obese as determined by their BMI and/or BMI z score	3 years
Secondary	Other allergic sensitisations	Between group differences in proportion of children with SPT sensitisation to additional food allergens (hazelnut, brazil nut, cashew, almond and walnut) and aero-allergens (timothy grass, birch pollen, house dust mite, cat and dog dander).	3 years
Secondary	Mechanisms of allergy	Between group differences in specific IgE, IgG and IgG4 to peanut, egg, sesame and aeroallergens	3 years
Secondary	Coeliac disease	Between group differences in prevalence of coeliac disease using coeliac antibody test (tTG IgA) screening test	3 years
Secondary	Atopic dermatitis	Between group differences in prevalence of atopic dematitis	3 years
Secondary	Allergic rhinoconjunctivitis	Between group differences in prevalence of seasonal and perennial rhinoconjunctivitis	3 years
Secondary	Asthma	Between group differences in prevalence of asthma	3 years
Secondary	Oral allergy syndrome	Between group differences in prevalence of oral allergy syndrome	3 years
Secondary	Parent reported food allergy	Between group differences in food reaction history (parent-reported immediate onset food allergy)	3 years
Secondary	Sibling allergies	Prevalence of sibling allergies (food allergies, eczema, asthma and rhinitis)	3 years
Secondary	AGE Level in association with food allergies	Between group differences in AGE levels in association with food allergies	3 years
Secondary	Skin fold thickness	Between group differences in skin fold thickness (triceps and subscapular)	3 years
Secondary	Circumference measurements	Between group differences in midarm, waist and head circumference	3 years
Secondary	Anthropometric ratios	Between group differences in; adjusted weight for height; waist; height ratio; height adjusted weight circumference	3 years
Secondary	Fat free mass	Between group differences in fat free mass	3 years
Secondary	Conicity index	Between group differences in conicity index (calculated from waist circumference and height and weight measurements)	3 years
Secondary	Cardiovascular health	Between group differences in the proportion of children with cardiovascular measurements outside the expected range	3 years
Secondary	Vascular stiffness	Between group differences in vascular stiffness	3 years
Secondary	AGE	Between group differences in advanced glycation end products (AGE)	3 years
Secondary	Inflammation	Between group differences in inflammation (measured using IL=6; sensitive CRP; TNF alpha; MCP-1; RANTES chemokine	3 years
Secondary	Metabolic and endocrine	Between group differences in insulin, IGF-1 and leptin	3 years
Secondary	White cell count	Between group differences in total white blood cell count	3 years
Secondary	Macronutrient dietary intake	Between group differences in macronutrient intake	3 years
Secondary	Dietary habits	Between group differences in fussy eating	3 years
Secondary	Physical activity	Influence of physical activity on anthropometry and body composition measurements	3 years
Secondary	Genetic influences	Influence of parental size on: height; weight; waist circumference on participant's size	3 years