Melbourne Infant Study - Bacille Calmette Guérin (BCG) for Allergy & Infection Reduction

Allergy Clinical Trial

— MIS BAIR  

Official title:

A Randomised, Controlled Trial to Determine if BCG Immunisation at Birth Reduces Allergy and Infection in Infants

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01906853
• Other study ID #: BCG12/01
• Secondary ID: 1051228
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 2013
• Est. completion date: June 30, 2024

Study information

• Verified date: January 2024
• Source: Murdoch Childrens Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. To determine if BCG immunisation at birth, compared to no BCG immunisation, leads to a reduction in measures of allergy and infection in the first 12 months of life.

2. To evaluate the immunological mechanisms underlying the non-specific effects of BCG by comparing markers of immunity between the BCG and non-BCG groups.

Description:

There has been a dramatic rise in allergic diseases worldwide since the 1980s. Asthma rates increased first, followed by eczema, allergic rhinitis and, more recently, food allergy - especially in infants and young children. In Australia, the prevalence of allergic disease is particularly high: up to 30% of children are affected, and eczema and asthma are among the most common chronic diseases of childhood.

Preventing allergic disease by an immunomodulatory intervention early in life would be a major advance with significant implications for individual health and public health resources. Bacillus Calmette-Guérin (BCG) immunisation is a potential intervention with an established safety profile. This vaccine has powerful non-specific effects on the cellular immune response that potentially prime host immunity away from an allergic pathway. Observational data and one small randomised controlled trial (RCT) suggest that BCG immunisation at birth leads to a substantial reduction in allergic disease - however, there is an absence of level 1 evidence.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1272
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 10 Days

Eligibility

Inclusion criteria:

• Less than 10 days old;

• English speaking mother;

• An informed consent form must be signed and dated by their parent(s) or legally acceptable representative after the nature of the study has been explained and prior to any study assessments/procedures;

• The infant's mother has screened negative for HIV during this pregnancy;

• Born no earlier than eight weeks before estimated date of delivery;

• Birth weight >1500g.

• The legal guardian expects to be able to complete four online/phone questionnaires over the infant's first 12 months of life and for the infant to be available for skin prick testing at RCH between 12-16 months of age.

Exclusion criteria:

• Any indication for BCG immunisation in the first 12 months of life including:

• likely travel to a high tuberculosis (TB) incidence country in the first year of life.

• Aboriginal and Torres Strait Islander babies living in parts of Australia where the incidence of TB is higher

• newborn babies, if either parent has leprosy or a family history of leprosy

• newborn in contact with a patient with TB.

• Known or suspected HIV infection

• Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor-alpha (TNF-alpha) (e.g. infliximab, etanercept, adalimumab).

• Born to a mother treated with bDMARDS (e.g. TNF-alpha blocking monoclonal antibodies) in the 3rd trimester;

• Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway;

• Malignancies involving bone marrow or lymphoid systems;

• Serious underlying illness including severe malnutrition;

• Medically unstable;

• Generalised septic skin disease and skin conditions such as eczema, dermatitis and psoriasis;

• Significant febrile illness;

• Mother immunosuppressed;

• Family history of immunodeficiency;

• Consanguineous parents;

• Multiple births more than twins.

Related Conditions & MeSH terms

• Allergy
• Communicable Diseases
• Eczema
• Hypersensitivity
• Infections
• Respiratory Tract Infections

Intervention

Biological:
• BCG

Locations

Country	Name	City	State
Australia	Mercy Hospital for Women	Heidelberg	Victoria
Australia	Royal Children's Hospital	Melbourne	Victoria

Sponsors (4)

Lead Sponsor	Collaborator
Murdoch Childrens Research Institute	Mercy Hospital for Women, Australia, Royal Children's Hospital, University of Melbourne

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect of sex on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of maternal BCG on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of presence or absence BCG scar on the non-specific effects of BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of timing of BCG administration on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of mode of delivery on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of family history of allergy on the allergy and eczema outcomes	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of season of birth on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Effect of hepatitis B vaccine timing birth on the non-specific effects BCG	Sub-group analysis	0-12 months and 0-5 years of age
Other	Meta-analysis	Joint meta-analysis with data from the Danish Calmette study (NCT01694108)	36 months
Other	Morbidity	Hospital admissions for any reason by parental report	0-12 months of age
Other	Morbidity	Hospital admissions for any reason by parental report	0-5 years of age
Primary	Atopic sensitisation measured by skin prick test (SPT)	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens	1 year of age
Primary	Atopic sensitisation measured by skin prick test (SPT)	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens	5 years of age
Primary	Lower respiratory tract infection (LRTI)	Measured by parent report	0-12 months
Primary	Lower respiratory tract infection (LRTI) hospital admissions	Proportion of participants with =1 hospital admission for LRTI reported by parent	0-5 years of age
Primary	Eczema ever	Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms	0-12 months
Primary	Eczema ever	Proportion of participants with eczema measured by Williams' UK diagnostic criteria using parental report of symptoms	0-5 years of age
Primary	Current asthma	Using ISAAC definitions	5 years of age
Primary	Asthma ever	Using ISAAC definitions	5 years of age
Secondary	Clinical food allergy	Proportion of participants with challenge-proven food allergy OR convincing history of food allergy in participants with a SPT wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food allergens	1 year of age
Secondary	Clinical food allergy	Proportion of participants with challenge-proven food allergy OR convincing history of food allergy in participants with a SPT wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food allergens	5 years of age
Secondary	Atopic sensitisation measured by SPT using a more stringent cut-off	Proportion of participants with a positive SPT defined as wheal diameter =3 mm greater than negative control at 15 min to one or more of a panel of food allergens and aeroallergens	1 year of age
Secondary	Atopic sensitisation measured by SPT using a more stringent cut-off	Proportion of participants with a positive SPT defined as wheal diameter =3 mm greater than negative control at 15 min to one or more of a panel of food allergens and aeroallergens	5 years of age
Secondary	Atopic sensitisation to multiple allergens measured by SPT	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to two or more of a panel of food allergens and aeroallergens	1 year of age
Secondary	Atopic sensitisation to multiple allergens measured by SPT	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to two or more of a panel of food allergens and aeroallergens	5 years of age
Secondary	Parent report of food allergy	Proportion of participants with an allergic reaction to any food reported by parent	0-12 months of age
Secondary	Parent report of food allergy	Proportion of participants with an allergic reaction to any food reported by parent	0-5 years of age
Secondary	Egg sensitisation	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to egg allergen	1 year of age
Secondary	Egg sensitisation	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to egg allergen	5 years of age
Secondary	Egg allergy	Proportion of participants with a challenge-proven egg allergy OR convincing history of egg allergy in participants with a SPT wheal diameter =2 mm greater than negative control at 15 min to egg	1 year of age
Secondary	Egg allergy	Proportion of participants with a challenge-proven egg allergy OR convincing history of egg allergy in participants with a SPT wheal diameter =2 mm greater than negative control at 15 min to egg	5 years of age
Secondary	Atopic wheeze	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens together with parent-reported wheeze	1 year of age
Secondary	Atopic wheeze	Proportion of participants with a positive SPT defined as wheal diameter =2 mm greater than negative control at 15 min to one or more of a panel of food and aeroallergens together with parent-reported wheeze	5 years of age
Secondary	Lower respiratory tract infection (LRTI)	Proportion of participants with =1 episode of LRTI, by parental report	Prior to first Diphtheria, Tetanus, Pertussis (DTP) vaccination
Secondary	Lower respiratory tract infection (LRTI)	Proportion of participants with =1 episode of LRTI, by parental report	0-5 years of age
Secondary	Rate of lower respiratory tract infection (LRTI)	Number of clinical episodes of LRTI, by parental report	0-12 months
Secondary	Rate of lower respiratory tract infection (LRTI)	Number of clinical episodes of LRTI, by parental report	Prior to first DTP vaccination
Secondary	Rate of lower respiratory tract infection (LRTI)	Number of clinical episodes of LRTI, by parental report	0-5 years of age
Secondary	Infections	Hospital admissions for any infection by parental report	0-12 months
Secondary	Infections	Hospital admissions for any infection by parental report	Prior to first DTP vaccination
Secondary	Infections	Hospital admissions for any infection by parental report	0-5 years of age
Secondary	Hospitalisation for respiratory tract infection (RTI)	Proportion of participants with =1 hospital admission for a RTI, by parent report	0-12 months of age
Secondary	Hospitalisation for respiratory tract infection (RTI)	Proportion of participants with =1 hospital admission for a RTI, by parent report	Prior to first DTP vaccination
Secondary	Hospitalisation for respiratory tract infection (RTI)	Proportion of participants with =1 hospital admission for a RTI, by parent report	0-5 years of age
Secondary	Rate of any infection	Number of clinical episodes of where an infant had symptoms of: wheeze, rattle/rattly chest, fever, runny/blocked nose, cough, or diarrhoea (with vomiting), by parent report	0-12 months of age
Secondary	Rate of any infection	Number of clinical episodes of where an infant had symptoms of: wheeze, rattle/rattly chest, fever, runny/blocked nose, cough, or diarrhoea (with vomiting), by parent report	Prior to first DTP vaccination
Secondary	Rate of upper respiratory tract infection (URTI)	Number of clinical episodes of upper respiratory tract infections, by parent report	0-12 months of age
Secondary	Rate of upper respiratory tract infection (URTI)	Number of clinical episodes of upper respiratory tract infections, by parent report	Prior to first DTP vaccination
Secondary	Rate of fever	Number of clinical episodes of fever, by parent report	0-12 months of age
Secondary	Rate of fever	Number of clinical episodes of fever, by parent report	Prior to first DTP vaccination
Secondary	Diarrhoea	Proportion of participants with =1 episodes of diarrhoea	0-12 months of age
Secondary	Diarrhoea	Proportion of participants with =1 episodes of diarrhoea	Prior to first DTP vaccination
Secondary	Rash with fever	Proportion of participants with =1 episodes of rash with fever	0-12 months of age
Secondary	Rash with fever	Proportion of participants with =1 episodes of rash with fever	Prior to first DTP vaccination
Secondary	Eczema ever	Proportion of participants with eczema measured by a combined eczema measure	0-12 months of age
Secondary	Eczema ever	Proportion of participants with eczema measured by a combined eczema measure	0-5 years of age
Secondary	Eczema	Proportion of clinician-diagnosed eczema, by parental report	0-12 months
Secondary	Eczema	Proportion of clinician-diagnosed eczema, by parental report	0-5 years of age
Secondary	Eczema onset	Age of onset of eczema, by parental report	0-12 months
Secondary	Eczema onset	Age of onset of eczema, by parental report	0-5 years of age
Secondary	Eczema severity	Measured by parental report (POEM score)	0-12 months
Secondary	Eczema severity	Measured by clinical assessment (SCORAD)	0-12 months
Secondary	Eczema severity	Eczema medication use, by parental report	0-12 months
Secondary	Eczema severity	Measured by parental report (POEM score)	0-5 years of age
Secondary	Eczema severity	Measured by clinical assessment (SCORAD)	0-5 years of age
Secondary	Eczema severity	Eczema medication use, by parental report	0-5 years of age
Secondary	Asthma severity	Measured by asthma control test (ACT), by parental/participant report	4 years of age
Secondary	Asthma severity	Measured by asthma control test (ACT), by parental/participant report	5 years of age
Secondary	Asthma severity	Hospital admissions for asthma, by parental report	2-5 years of age
Secondary	Laboratory measures of the immune response		Time Frame: 0-5 years of age