Microbiome and Immune Profiling in Infant With Cow's Milk Allergy

NCT05178004 | Unknown

• 1 other identifier: R&D GN18GA334P
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Non-IgE-mediated cow's milk allergy (CMPA) is associated to gastrointestinal symptoms, and its cause remains poorly understood, limiting the identification of specific markers to help with the diagnosis. Using a non-invasive method, the aim of this study is to identify new protein markers as well as to profile the bacteria (germs) released in stools of infants during the inflammatory process of this condition (acute and recovery phase). The study group will include infants who are born at term by an uncomplicated birth and diagnosed with non-IgE-mediated CMPA in the first 4 months of life, while the control groups will consist of infants either healthy or infants diagnosed with IgE-mediated CMPA or with a non-allergic gastrointestinal inflammatory condition (NAGIC). All groups will be matched for age, gender, type of feeding and mode of delivery. Stool, urine and blood samples (the latter only if already taken during the hospital admission in severe cases) will be collected at the acute and the recovery phase of this condition while the patient follows a diary free diet (breast milk or hypoallergenic formula milk). Protein markers, bacteria and their products will be measured in stool, urine and blood samples. These measurements will be carried out at the University of Glasgow, Human Nutrition Section labs at Glasgow Royal Infirmary and other University of Glasgow research labs as required. The ultimate aim is to explore the potential role of immune protein markers and bacteria in stools and urine and their possible use in diagnosing the condition non-invasively. Further understanding of the disease's cause may contribute to the development of new infant feed that could provide gut protection.

Conditions

Cow Milk Allergy

Outcome Measures

Primary Outcomes (5)

• Microbiome profiling

  Gut bacterial diversity in infants with non-IgE-mediated CMPA compared to control groups, assessed by 16s rRNA sequencing (at baseline and throughout the study period).

  32 months

• Faecal metabolites

  The concentration of faecal metabolites in infants with non-IgE-mediated CMPA compared to control groups.

  32 months

• Urine metabolites

  The concentration of urine metabolites in infants with non-IgE-mediated CMPA compared to control groups.

  32 months

• Immune profiling

  Concentration of faecal inflammatory proteins in infants with non-IgE-mediated CMPA compared to control groups.

  32 months

• Analysis of faecal microbiome to diagnose non-IgE-mediated CMPA

  The use of gut microbiome changes in non-IgE-mediated CMPA as a tool in confirming the diagnosis of mild, moderate, and severe non-IgE mediated CMPA

  32 months

Secondary Outcomes (5)

• Assessment of clinical symptoms

  32 months

• Inflammatory markers and clinical symptoms

  32 months

• Acute vs Chronic non-IgE-mediated CMPA

  32 months

• Effect of Hypoallergenic formula milks on gut microbiome

  32 months

• Effect of Hypoallergenic formula milks on inflammatory markers

  32 months

Study Arms (4)

Non-IgE-mediated CMPA

Infants with mild, moderate and severe non-IgE-mediated cow's milk protein allergy

Other: Faecal and Urine sample collection

IgE-mediated CMPA

Infants with IgE-mediated CMPA

Other: Faecal and Urine sample collection

Healthy

Healthy infants who have never shown signs of cow's milk protein allergy

Other: Faecal and Urine sample collection

Non allergic gastrointestinal conditions

Infants with suspected cow's milk allergic at enrolment and ruled out following Oral Food Challenge

Other: Faecal and Urine sample collection

Interventions

Faecal and Urine sample collection OTHER

This is an observational study.

Healthy; IgE-mediated CMPA; Non allergic gastrointestinal conditions; Non-IgE-mediated CMPA

Eligibility Criteria

• Age: Up to 16 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

60 infants clinically diagnosed with non-IgE-mediated CMPA by primary and secondary care professionals presenting mainly with gastrointestinal symptoms (Gastro-oesophageal symptoms, diarrhoea and blood in the stools) while on enteral feeds (breast or formula milk). 60 healthy infants will be recruited from the same population, independently of levels of CMP exposure. Healthy infants will be matched for age, gender, and type of birth with allergic infants, allowing variables to be examined between cases and controls. Additionally, 30 infants with IgE-mediated CMPA, confirmed by SPT or positive CMP-specific IgE will be recruited. Lastly, all Non-Allergic GastroIntestinal Conditions (NAGIC cases), for whom non-IgE-mediated CMPA was ruled out following an OFC will be included in the study as a reference group. The number of NAGIC cases will depend on the recruitment numbers and the appropriate use of the diagnostic clinical criteria.

You may qualify if:

• Infants ≤4 months (prior to weaning)
• Infants born at term (≥37and ≤42weeks), by uncomplicated normal birth or caesarean section and appropriately grown for gestational age.

You may not qualify if:

• Infants who present with pre-existing risk factors for altered intestinal perfusion, among others intrauterine growth restriction, birth asphyxia, exchange transfusion, cyanotic congenital heart disease or polycythemia as these infants are at increased risk of necrotizing enterocolitis.
• Other congenital malformations (chest and abdomen) and infections (such as HIV, hepatitis B and C)
• Those who received antibiotics or need endotracheal, feeding or suctioning tubes will also be excluded as these manipulations could result in modification of microbial flora and could have an impact in intestinal development.
• Participants whose parents/carers cannot speak or understand English will be excluded from the study.

Sponsors & Collaborators

• University of Glasgow: lead
• NHS Greater Glasgow and Clyde Board HQ: collaborator
• Nutricia, Inc.: collaborator

Study Sites (1)

Glasgow Royal Hospital for Children

Glasgow, Scotland, G51 4TF, United Kingdom

RECRUITING

Related Publications (3)

• Venter C, Brown T, Shah N, Walsh J, Fox AT. Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy - a UK primary care practical guide. Clin Transl Allergy. 2013 Jul 8;3(1):23. doi: 10.1186/2045-7022-3-23.

  PMID: 23835522 BACKGROUND

• Leonard SA, Nowak-Wegrzyn A. Food protein-induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol. 2011 Aug;107(2):95-101; quiz 101, 162. doi: 10.1016/j.anai.2011.06.004.

  PMID: 21802016 BACKGROUND

• Claud EC. Neonatal Necrotizing Enterocolitis -Inflammation and Intestinal Immaturity. Antiinflamm Antiallergy Agents Med Chem. 2009 Sep;8(3):248-259. doi: 10.2174/187152309789152020.

  PMID: 20498729 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Faecal, urine and blood samples

MeSH Terms

Conditions

Milk Hypersensitivity

Interventions

Defecation

Condition Hierarchy (Ancestors)

Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Officials

• George Raptis

  NHS Greater Glasgow and Clyde

  PRINCIPAL INVESTIGATOR

Central Study Contacts

George Raptis

CONTACT

01414516491; george.raptis@nhs.net

Konstantinos Gerasimidis

CONTACT

01412018689; konstantinos.gerasimidis@glasgow.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant in Paediatric Allergy

Study Record Dates

• First Submitted: March 19, 2021
• First Posted: January 5, 2022
• Study Start: August 1, 2018
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)