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

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

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.

Study Overview

• Status: Completed
• Conditions: Food Allergy
• Intervention / Treatment: Other: SLIT to cow's milk; Other: Conventional OIT to cow's milk; Other: Low dose OIT

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Niño Jesus Hospital
• United Kingdom
  • London, United Kingdom
    • Imperial College London / Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SLIT followed by Conventional OIT; Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk	Other: SLIT to cow's milk; Sublingual immunotherapy; Other: Conventional OIT to cow's milk; Oral Immunotherapy
Active Comparator: Conventional OIT; Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk	Other: Conventional OIT to cow's milk; Oral Immunotherapy; Other: Low dose OIT; Oral Immunotherapy (low dose)
Placebo Comparator: Delayed start OIT; Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk	Other: Conventional OIT to cow's milk; Oral Immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of adverse events	Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)	1 year
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
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
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
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
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
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
Immunological outcomes: Allergen-specific IgE	Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy	12 months
Peptide microarray	Trend in CM-peptide binding during OIT	12 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: JP Moulton Charitable Foundation; Sociedad Española de Alergología e Inmunología; Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica

Publications and helpful links

General Publications

• Turner PJ, Duca B, Chastell SA, Alvarez O, Bazire R, Vazquez-Ortiz M, Rodriguez Del Rio P. IgE-sensitization predicts threshold but not anaphylaxis during oral food challenges to cow's milk. Allergy. 2022 Apr;77(4):1291-1293. doi: 10.1111/all.15195. Epub 2021 Dec 14. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): January 19, 2022

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 11, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 14, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Desensitisation; Cow's milk allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: 18SM4569; 18/LO/1070 (Other Identifier: NHS Human Research Authority)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No