Food AllergySOCMANCT02216175
Improving the Safety of Oral Immunotherapy for Cow's Milk Allergy
A study testing SLIT to cow's milk, Low dose OIT and Conventional OIT to cow's milk in people with Food Allergy, run by Imperial College London at 2 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Food Allergy
- What is being tested?
- SLIT to cow's milk, Low dose OIT and Conventional OIT to cow's milk
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 19 Jul 2018to 19 Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to randomisation
- Informed consent of parent/legal guardian, patient assent where possible
Who cannot join
- Required previous admission to an intensive care unit for management of an allergic reaction.
- Significant symptoms of non---IgE---mediated CM allergy within the previous 12 months.
- 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).
- 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.
- 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)
- Clinically significant chronic illness (other than asthma, rhinitis or eczema)
Show all 11Show fewer
- History of symptoms of eosinophilic oesophagitis, irrespective of cause
- Undergoing specific immunotherapy to another allergen and within the first year of treatment.
- Receiving anti--IgE therapy, oral immunosuppressants, beta---blocker or ACE inhibitor.
- Pregnancy
- Unwilling or unable to fulfil study requirements
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
Imperial College London / Imperial College Healthcare NHS Trust
London
About this study
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
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.
- Conditions
- Food Allergy
- Being tested
- SLIT to cow's milk, Low dose OIT, Conventional OIT to cow's milk
- Keywords
- Cow's milk allergy, Desensitisation, Safety
- Medical subject headings
- Food Hypersensitivity, Milk Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SLIT to cow's milkOther
Sublingual immunotherapy
Low dose OITOther
Oral Immunotherapy (low dose)
Conventional OIT to cow's milkOther
Oral Immunotherapy
| Study group | Role | What they receive |
|---|---|---|
| SLIT followed by Conventional OIT | Experimental | Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk Receives: Other: SLIT to cow's milk; Other: Conventional OIT to cow's milk |
| Conventional OIT | Active comparator | Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk Receives: Other: Low dose OIT; Other: Conventional OIT to cow's milk |
| Delayed start OIT | Placebo comparator | Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk Receives: Other: Conventional OIT to cow's milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (10)
Incidence of adverse events
Incidence of adverse events experienced (including rate of withdrawals, and anaphylaxis/adrenaline use during updosing)
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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
Measured: 12 months
Immunological outcome: skin prick test
Change in skin prick test wheal (mm) and end-point titration skin prick test between baseline and post immunotherapy
Measured: 12 months
Immunological outcomes: Allergen-specific IgE
Change in allergen-specific IgE (KuA/l) between baseline and post immunotherapy
Measured: 12 months
Peptide microarray
Trend in CM-peptide binding during OIT
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study start19 Jul 2018
- Primary completion30 Sep 2021
- Study completion19 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Food AllergyStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- JP Moulton Charitable Foundation, Sociedad Española de Alergología e Inmunología, Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica
- Responsible party
- Principal investigator, Paul Turner, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02216175
- Sponsor's protocol ID
- 18SM4569
- Other IDs
- 18/LO/1070
- Acronym
- SOCMA
- Status last verified
- Jan 2023
- First submitted
- 7 Aug 2014
- Last updated
- 18 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 34874567
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02216175
- Acronym / sponsor ID
- SOCMA / 18SM4569
- Conditions
- Food Allergy
- Keywords
- Cow's milk allergy, Desensitisation, Safety
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- JP Moulton Charitable Foundation, Sociedad Española de Alergología e Inmunología, Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica
- Study start
- 19 Jul 2018 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SLIT followed by Conventional OIT | Experimental | Other: SLIT to cow's milk, Other: Conventional OIT to cow's milkParticipants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk |
| Conventional OIT | Active comparator | Other: Low dose OIT, Other: Conventional OIT to cow's milkParticipants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk |
| Delayed start OIT | Placebo comparator | Other: Conventional OIT to cow's milkParticipants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to randomisation
- Informed consent of parent/legal guardian, patient assent where possible
Key exclusion criteria (11 listed)
- Required previous admission to an intensive care unit for management of an allergic reaction.
- Significant symptoms of non---IgE---mediated CM allergy within the previous 12 months.
- 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).
- 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.
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SLIT to cow's milkSublingual immunotherapy | Other | SLIT followed by Conventional OIT |
| Low dose OITOral Immunotherapy (low dose) | Other | Conventional OIT |
| Conventional OIT to cow's milkOral Immunotherapy | Other | Conventional OIT, Delayed start OIT, SLIT followed by Conventional OIT |
Primary outcome
Adverse events in participants
Time frame: 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.
10 secondary outcomes
Incidence of adverse events
Time frame: 1 year
Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy
Time frame: 1 year
Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy
Time frame: 15 months
Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy
Time frame: 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
Time frame: 15 months
Change in self-efficacy after each phase of immunotherapy
Time frame: 15 months
Immunological outcomes
Time frame: 12 months
Immunological outcome: skin prick test
Time frame: 12 months
Immunological outcomes: Allergen-specific IgE
Time frame: 12 months
Peptide microarray
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Derived from this study: PubMed 34874567Turner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SLIT to cow's milk, Low dose OIT and Conventional OIT to cow's milk in people with Food Allergy, run by Imperial College London at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events in participants (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02216175, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.