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

Not Applicable

Completed

• Conditions: Food Allergy
• Interventions: Other: Conventional OIT to cow's milk; Other: SLIT to cow's milk; Other: Low dose OIT

• Registration Number: NCT02216175
• Lead Sponsor: Imperial College London

Brief 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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-08-07
• Study First Submitted QC: 2014-08-11
• Study First Posted: 2014-08-13
• Study Start: 2018-07-19
• Primary Completion: 2021-09-30
• Study Completion: 2022-01-19
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-14
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Delayed start OIT	Conventional OIT to cow's milk	Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk
Conventional OIT	Conventional OIT to cow's milk	Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk
SLIT followed by Conventional OIT	SLIT to cow's milk	Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk
SLIT followed by Conventional OIT	Conventional OIT to cow's milk	Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk
Conventional OIT	Low dose OIT	Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk

Primary Outcome Measures

Name	Time	Method
Adverse events in participants	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Change in Health-related quality of life (HRQL) from baseline - assessed using Change in EQ-5D from baseline - after each phase of immunotherapy	15 months	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.
Immunological outcomes: Allergen-specific IgE	12 months	Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy
Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy	1 year	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
Immunological outcomes	12 months	Change in skin prick test wheal (mm), end-point titration skin prick test, allergen-specific IgE (KuA/l) between baseline and post immunotherapy
Immunological outcome: skin prick test	12 months	Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy
Peptide microarray	12 months	Trend in CM-peptide binding during OIT
Incidence of adverse events	1 year	Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)
Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy	15 months	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)
Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy	15 months	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)
Change in self-efficacy after each phase of immunotherapy	15 months	Change in self-efficacy at 6, 12 and 15 months from baseline, as assessed in study participants and their parent/carer using validated questionnaire.

Trial Locations

Locations (2)

Niño Jesús Hospital; 🇪🇸 Madrid, Spain

Imperial College London / Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom