Improving the Safety of Oral Immunotherapy for Cow's Milk Allergy

Food Allergy Clinical Trial

— SOCMA  

Official title:

Phase 2/3 Clinical Trial to Assess the Effect of a Sublingual Treatment Phase Prior to Oral Immunotherapy in Children With Cow's Milk Allergy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02216175
• Other study ID #: 18SM4569
• Secondary ID: 18/LO/1070
• Status: Completed
• Phase: N/A
• Start date: July 19, 2018
• Est. completion date: January 19, 2022

Study information

• Verified date: January 2023
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Allergy to cow's milk is the most common food allergy affecting children. There is currently no accepted routine clinical therapy to cure milk allergy. Recently studies have attempted to induce desensitisation using small daily doses of cow's milk, predominantly by the oral route (oral immunotherapy, OIT). Although this therapy works for some people, its effects are not generally long lasting and it is associated with significant side effects during protocol, including potentially life-threatening allergic reactions. Pilot data suggests that sublingual immunotherapy (SLIT, where allergen is held under the tongue, rather than swallowed) can also induce a degree of desensitisation, but with fewer adverse events. However, the degree of desensitisation induced appears to be lower than that with oral immunotherapy. The investigators wish to determine whether a sublingual pretreatment phase can improve the safety of conventional OIT in cow's milk allergy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 19, 2022
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

1. Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to randomisation

2. Informed consent of parent/legal guardian, patient assent where possible

Exclusion Criteria:

1. Required previous admission to an intensive care unit for management of an allergic reaction.

2. Significant symptoms of non---IgE---mediated CM allergy within the previous 12 months.

3. Children with a past history of CM allergy currently consuming CM-containing products other than extensively--heated milk in baked foods (e.g. biscuits, cakes).

4. Poorly controlled asthma within the previous 3 months (as defined by clinician judgement with reference to the ICON consensus), or asthma requiring treatment with >5 days oral corticosteroids within the previous 3 months.

5. Moderate---severe eczema, defined as requiring more than once daily application of 1% hydrocortisone as maintenance treatment despite appropriate use of emollients (eczema is not otherwise an exclusion criteria)

6. Clinically significant chronic illness (other than asthma, rhinitis or eczema)

7. History of symptoms of eosinophilic oesophagitis, irrespective of cause

8. Undergoing specific immunotherapy to another allergen and within the first year of treatment.

9. Receiving anti--IgE therapy, oral immunosuppressants, beta---blocker or ACE inhibitor.

10. Pregnancy

11. Unwilling or unable to fulfil study requirements

Related Conditions & MeSH terms

• Food Allergy
• Food Hypersensitivity
• Hypersensitivity
• Milk Hypersensitivity

Intervention

Other:
• SLIT to cow's milk
Sublingual immunotherapy
• Low dose OIT
Oral Immunotherapy (low dose)
• Conventional OIT to cow's milk
Oral Immunotherapy

Locations

Country	Name	City	State
Spain	Niño Jesús Hospital	Madrid
United Kingdom	Imperial College London / Imperial College Healthcare NHS Trust	London

Sponsors (4)

Lead Sponsor	Collaborator
Imperial College London	JP Moulton Charitable Foundation, Sociedad Española de Alergología e Inmunología, Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica

Countries where clinical trial is conducted

Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events in participants	Proportion of participants experiencing adverse events (excluding mild, non-transient symptoms) conventional OIT to cow's milk in phase 2, in those who have received SLIT pretreatment compared to placebo.	1 year
Secondary	Incidence of adverse events	Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)	1 year
Secondary	Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy	Efficacy defined at Double-blind, placebo-controlled food challenge (DBPCFC) as the proportion of study participants experiencing: No symptoms (or only mild transient symptoms) to 8 grams CM protein (approx. 250mls fresh milk) ("Complete desensitisation"); No symptoms (or only mild transient symptoms) to at least 1.4 grams CM protein (approx. 45mls fresh milk) ("Partial desensitisation"); At least a 10--fold increase in eliciting dose (defined as the lowest dose which elicits objective symptoms or signs at challenge). …at 6 and 12 months in the different treatment groups	1 year
Secondary	Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy	Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire: - Food Allergy Quality of Life Questionnaires (FAQLQ)	15 months
Secondary	Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy	Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire: - Food Allergy Independent Measure (FAIM)	15 months
Secondary	Change in Health-related quality of life (HRQL) from baseline - assessed using Change in EQ-5D from baseline - after each phase of immunotherapy	Change in HRQL measures at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using the following validated questionnaire: - EQ-5D - a standardized instrument for use as a measure of health outcome.	15 months
Secondary	Change in self-efficacy after each phase of immunotherapy	Change in self-efficacy at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using validated questionnaire.	15 months
Secondary	Immunological outcomes	Change in skin prick test wheal (mm), end-point titration skin prick test, allergen-specific IgE (KuA/l) between baseline and post immunotherapy	12 months
Secondary	Immunological outcome: skin prick test	Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy	12 months
Secondary	Immunological outcomes: Allergen-specific IgE	Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy	12 months
Secondary	Peptide microarray	Trend in CM-peptide binding during OIT	12 months