Probiotics in paediatric patients with an allergy to cow’s milk proteins

ISRCTN	ISRCTN69069358
DOI	https://doi.org/10.1186/ISRCTN69069358
Secondary identifying numbers	07/2016

Submission date: 18/11/2021
Registration date: 29/12/2021
Last edited: 27/03/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Background and study aims
An allergy to cow’s milk proteins is one of the most frequent food allergies during early childhood. It is not completely known how it develops, although changes in intestinal microflora (bacteria) have been found to influence immune tolerance to milk proteins. Probiotics (live bacteria and yeasts) have been proposed for the treatment and prevention of food allergies. The aim of this study is to investigate the anti-allergenic effect of a mixture of three Bifidobacterium strains in children with an allergy to cow’s milk proteins before and after a 45-day treatment.

Who can participate?
Children aged 6-12 months with an allergy to cow’s milk proteins on a cow’s milk protein exclusion diet

What does the study involve?
All participants receive the same treatment. Following the initial visit, the children start a commercially available extensively hydrolyzed casein (protein) formula and treatment with the probiotic mixture for 45 days. Blood samples are collected soon before the probiotic treatment and at the end of the probiotic supplementation. After 45 days from the suspension of the probiotic, while the participants are still on a milk protein elimination diet, another blood sample is collected to better understand the specific effects of Bifidobacterium.

What are the possible benefits and risks of participating?
The Bifidobacteria could help increase tolerance to cow’s milk proteins and could provide a significant benefit in the treatment of cow’s milk protein allergy.

Where is the study run from?
University of Campania “Luigi Vanvitelli” (Italy)

When is the study starting and how long is it expected to run for?
January 2015 to April 2018

Who is funding the study?
AOU Università degli Studi della Campania Luigi Vanvitelli (Italy)

Who is the main contact?
Caterina Strisciuglio
caterina.strisciuglio@unicampania.it

Contact information

Prof Caterina Strisciuglio
Scientific

Via Luigi De Crecchio 4
Naples
80138
Italy

Phone	+39 (0)815665464
Email	caterina.strisciuglio@unicampania.it

Study information

Study design	Prospective non-randomized pilot trial
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	No participant information sheet available
Scientific title	Bifidobacteria improve immune tolerance in paediatric patients with an allergy to cow’s milk proteins
Study hypothesis	Many experimental and clinical studies have analyzed the role of probiotics in the prevention and treatment of allergic diseases but only a limited number of studies evaluated the in vivo probiotic effect on pediatric patients affected by the allergy to cow’s milk proteins (CMA). It is hypothesized that Bifidobacteria could have a beneficial effect on the acquisition of oral tolerance to cow's milk proteins.
Ethics approval(s)	Approved 16/12/2015, the Institutional Review Board of the University of Campania “Luigi Vanvitelli” (Via Santa Maria di Costantinopoli 104, 80138 Naples, Italy; +39 (0)815664008; comitatoetico@unicampania.it), ref: 07/2016
Condition	Cow's milk allergy
Intervention	Following the diagnosis of cow's milk allergy, the children start a commercially available extensively hydrolyzed casein formula (EHCF, Nutramigen, Mead Johnson, Rome, Italy) and treatment with the probiotic mixture for 45 days (5 billion colony-forming units/day (bnl CFU/die), specifically 3 bnl CFU/die of Bifidobacterium Longum BB536; 1 bnl CFU/die of Bifidobacterium Infantis M-63; 1 1 bnl CFU/die of Bifidobacterium breve M-16V). Blood samples are collected soon before the probiotic treatment (baseline, T0) and at the end of probiotic supplementation (T1). Further, after 45 days from the suspension of the probiotic, while the patients were still on a cow's milk protein elimination diet, another blood sample was collected to better understand the specific effects of Bifidobacterium (T2)
Intervention type	Supplement
Primary outcome measure	The frequency of various lymphocyte subsets in peripheral blood (e.g. T cells [CD3+, either the helper CD4+ and the cytotoxic CD8+ cells], and B cells [CD19+]) evaluated by flow cytometry at baseline, after 45 days of probiotic treatment (T1) and 45 days from the suspension of the treatment (T2)
Secondary outcome measures	The percentage of degranulation activity of circulating basophils evaluated in fresh blood samples using the basophilic activation test (BAT) after in vitro exposure to cow’s milk, casein, lactalbumin and lactoglobulin reported at baseline, at T1 and T2
Overall study start date	15/01/2015
Overall study end date	30/04/2018

Eligibility

Participant type(s)	Patient
Age group	Child
Sex	Both
Target number of participants	10
Total final enrolment	8
Participant inclusion criteria	Paediatric patients with an allergy to cow’s milk proteins (CMA)
Participant exclusion criteria	1. Consumption of prebiotic or probiotic products, and/or antibiotics in the previous 4 weeks 2 . A history of cow’s milk-induced anaphylaxis 3. Eosinophilic disorders of the gastrointestinal tract 4. Food protein-induced enterocolitic syndrome 5. Concomitant chronic systemic diseases 6. Other gastrointestinal disease
Recruitment start date	15/07/2016
Recruitment end date	30/07/2017

Locations

Countries of recruitment

Italy

Study participating centre

University of Campania “Luigi Vanvitelli”

Via Luigi De Crecchio, 4
Napoli
80138
Italy

Sponsor information

Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli
Hospital/treatment centre

Piazza Luigi Miraglia 2
Naples
80138
Italy

Phone	+39 (0)81 5661111
Email	dip.donnabambinoechirurgia@unicampania.it
Website	http://www.policliniconapoli.it/Home
"ROR"	https://ror.org/02p9ey581

Funders

Funder type

Hospital/treatment centre

Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli

No information available

Results and Publications

Intention to publish date	30/06/2022
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal. Additional documents (such as study protocol, statistical analysis plan etc) will be available.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Caterina Strisciuglio (caterina.strisciuglio@unicampania.it), including the demographic and clinical characteristics of the study population, and data from experiments carried out in the laboratory.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		23/03/2023	27/03/2023	Yes	No

Editorial Notes

27/03/2023: Publication reference added.
13/12/2021: Trial's existence confirmed by the Institutional Review Board of the University of Campania “Luigi Vanvitelli”.