Cow's Milk Protein Sensitivity Clinical Trial
Official title:
Efficacy and Safety of Specific Oral Tolerance Induction in Children Allergic to Cow's Milk Proteins According to Their Serum Specific IgE Level
Induction of oral tolerance in children allergic to cow's milk proteins is not risk-free.
The analysis of factors that may influence the outcome is of utmost importance.
The aim of the study is to analyse the efficacy and safety of the induction phase of oral
tolerance induction according to specific IgE level, as well as adverse events during the
maintenance phase.
Patients allergic to cow's milk are to be included in an oral tolerance induction protocol.
Patients will be grouped according to specific IgE levels in serum (ImmunoCAP) into group I
(sIgE<3.5 kU/L), II (sIgE 3.5-17 kU/L) and III (>17-50kU/L). Allergic children with similar
characteristics will included as a control group. Visits are established at 1, 6 and 12
months after the induction phase. Serum specific IgE levels to cow's milk and its proteins
will be determined at inclusion, and at 6 and 12 months visits after the induction phase.
Children allergic to cow's milk proteins (CMA) will be included. They have to be diagnosed
with CMA during the first year of life and have attended periodic follow-up visits to our
Allergy Clinic at Hospital La Paz (Madrid, Spain). Clinical data on personal history of
asthma, allergy to other foods and positive reactions upon cow's milk ingestion along with
their evolution from initial diagnosis will be recorded.
Prior to inclusion in the SOTI protocol, determination of serum specific IgE to cow's milk
(CM), ALA, BLG and casein (ImmunoCAP, Phadia, Uppsala, Sweden) will be performed and current
clinical status will be confirmed by oral food challenge (OFC) with cow's milk. An open OFC
with CM (3 g of proteins per 100 mL) will be performed following a modified protocol
according to the level of allergic sensitisation. Group I will start at a dose of 2 mL, and
those in groups II and III started at a dose of 0.005 mL. In both protocols doses will be
doubled until objective clinical reactivity is achieved.
Determination of serum specific IgE to cow's milk and its proteins will be performed in the
follow-up at 6 and 12 months visits.
In order to evaluate the influence of the level of sensitisation in the result of SOTI,
patients will be classified into three groups according to the level of sIgE for CM and/or
its proteins: group I (0.35-3.5 kU/L, CAP Class I and II); group II (>3.5-17 kU/L, CAP Class
III); group III (>17-50kU/L, CAP Class IV). The highest sIgE level against any of the CM or
its proteins will determine the group of inclusion.
A control group of cow's milk allergic children, with similar levels of sIgE, will be
included in order to evaluate the natural evolution to tolerance in CMA. They will be
followed for one year, after which, clinical reactivity with OFC will be again confirmed.
These control patients will selected among those who, after the initial OFC, refuse to
undergo SOTI.
Specific Oral Tolerance Induction:
The initial dose for SOTI will be the previous dose that elicited symptoms in the OFC. Group
I doses will be upped weekly in the hospital setting, and patients will maintain that dose
twice daily at home. Groups II and III also will start with the previous dose that elicited
symptoms in the OFC, but will receive incremental doses daily in the hospital setting until
they reach a dose of 1 mL. Achieving an intake of 200 mL of milk (6 g of proteins) twice a
day, which is the usual amount for patients of that age, will be considered complete
tolerance.
Reactions occurring during the induction phase at the hospital will be treated according to
the severity of symptoms. If patients present with mild non-objective symptoms, the same
dose will be repeated. If the reaction is objective and limited to local symptoms, the
previous dose will be given after the resolution of symptoms. If the reaction is
generalised, involving two organ systems, SOTI will be continued with a dose which is two
doses previous to the one that elicited symptoms. If the reaction involves three organ
systems, the next dose administered will be reduced three steps in the dosage protocol.
Written instructions will be given to parents regarding how to treat possible adverse
reactions at home.
After the induction phase, patients will continue to consume 200 mL milk twice daily and
dairy products were allowed freely.
In the maintenance phase, follow-up visits are scheduled at one month, six months and one
year after finishing the induction phase. Data on tolerance of cow's milk and dairy products
will be recorded. Adverse events upon ingestion will also be recorded.
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Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment