SOCMA
Research type
Research Study
Full title
Improving the safety of oral immunotherapy for cow's milk allergy (The SOCMA Study)
IRAS ID
174513
Contact name
Paul Turner
Contact email
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Research Summary
Cow's milk allergy is a leading cause of food allergy and severe allergic reactions in children. It impacts significantly on quality of life due to fear of reactions and diet/lifestyle restrictions needed to reduce this risk. Our aim is to develop a safe treatment for this condition.
One way to “re-train” the immune system not to react is to give increasing amounts of milk every day for several months; this is known as oral immunotherapy (OIT). An alternative is to keep the milk under the tongue for a few minutes every day, rather than simply swallow it. This approach, known as sublingual immunotherapy (SLIT), is effective for hayfever. OIT can be effective for milk allergy, but it can cause frequent reactions in some people. SLIT causes very few reactions but it doesn’t have as big an effect in changing the amount of milk tolerated after treatment. One study in peanut-allergic people has shown that reactions to OIT are largely reduced when SLIT is done first. We want to see whether using SLIT followed by OIT is a safer way of doing immunotherapy. We will also see if the SLIT dose must be kept under the tongue, or if a similar effect happens when the same dose is swallowed immediately.
To test this hypothesis, we will conduct a clinical trial in which milk-allergic children will be allocated at random (by a computer) to receive pretreatment for the first 6 months with either SLIT, OIT (using the same doses as in SLIT) or placebo. Then, all children will receive OIT for another 6 months. We will assess the safety of this approach as well as how the amount of milk a child can tolerate changes during the study. We will also assess impact on families’ quality of life, to see how these change during the study.
Summary of Results
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.
In the SOCMA study, we recruited 68 children and young people across 2 study sites (London, UK; Madrid, Spain). Participants underwent a double-blind, placebo-controlled food challenge, to confirm milk allergy and assess how much milk was needed to trigger an allergic reaction. They were then randomised to one of 3 treatment groups for 6 months of pretreatment: SLIT, OIT using the same doses as the SLIT group, or placebo. After 6 months, all participants then underwent OIT using an identical method.
At the end of the second 6 months, all participants underwent a further double-blind food challenge.Prior to immunotherapy, the median threshold causing an objective allergic reaction in study participants was 44mg milk protein, equivalent to 1.3ml of cow’s milk. After 6 months of pretreatment, this increased to 444mg protein (13ml of milk) in those on SLIT and 144mg protein in those receiving OIT (4.8ml of milk). There was no significant change in reaction threshold in the placebo group. After a further 6 months of OIT in all subjects, the average amount of milk protein triggering a reaction increased to 4444mg (130ml milk).
Evaluating adverse events during OIT treatment, 16% and 14% of doses in those receiving SLIT or OIT pretreatment were associated with (mostly mild) adverse events during OIT in the second half of the study. The equivalent rate in those who were in the placebo pretreatment group was 28%. Those given SLIT pretreatment had fever significant adverse events compared to those on OIT (1% of doses versus 2.4%).In summary, we found evidence for pretreatment with SLIT compared to the same dose administered by mouth in terms of both desensitisation and a more favourable safety profile for subsequent OIT. Further analyses are underway in terms of evaluating the safety data of both approaches in more detail, and possible predictors of outcome.
REC name
London - Central Research Ethics Committee
REC reference
18/LO/1070
Date of REC Opinion
13 Jul 2018
REC opinion
Further Information Favourable Opinion