Clinical trial NCT03819556: Swedish Study of Immunotherapy for Milk Allergy in Children
Official title: Swedish Study of Immunotherapy for Milk Allergy in Children
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Milk Allergy
Keywords: Cow milk allergy
Oral immune therapy
Basophil activation test
IgE
Microbiome
Quality of life
Lead sponsor: Umeå University
Sponsor class: OTHER
First posted: 2019-01-28
Enrollment: 80
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open randomized interventional study
Primary purpose: TREATMENT

Brief summary: This trial is a two-armed open randomized controlled trial in children aged 5-15 years with challenge proven Immunoglobulin E (IgE)-associated milk allergy.The purpose is to determine if oral immunotherapy with milk can induce tolerance to milk. The active intervention is intake of increasing amounts of fresh milk for six months followed by three years of maintenance treatment with milk. The control group continues their elimination (milk free) diet. The trial will recruit patients at ten pediatric departments in Sweden, coordinated by Umeå University. The primary outcome is milk tolerance (defined as a negative double-blind placebo-controlled milk challenge) at trial completion 3.5 years after start of treatment. Secondary outcomes include allergic symptoms during treatment documented as certain allergic manifestations, changes in immunological and microbial biomarkers, quality of life and nutritional status.

Detailed description: The underlying hypothesis is that exposure to milk in a controlled way can be delivered safely and induce tolerance to milk.The aim of this trial is to evaluate a specific protocol for oral milk intake to achieve sustainable tolerance.

Before randomization all patients are tested for milk allergy using a double-blind placebo-controlled milk challenge and baseline laboratory analyses (specific IgE). Patients with confirmed, challenge-proven milk allergy are randomized to oral immunotherapy (active group) or milk-free diet (control group).The active group will receive a stepwise increase in oral milk intake. The increased dose will be given in hospital outpatient clinics by experienced study staff following a standard protocol. All other doses are given att home where the patients have adrenaline ready to use. When the patient has reached a daily intake of 100 ml of milk without serious allergic reactions they will be maintained on this dosis for three years. At this stage (after finished dose escalation or after six months for the control group) the patients will be tested for the second set of laboratory analyses.

During maintenance, the patients in the active group are encouraged not to avoid milk protein and instead eat milk-containing food when it is offered. Patients in the control group receive standard care with exclusion of milk from their diet for the whole trial duration.

After three years of maintenance therapy for the active group, both groups avoid milk for one week and then undergo a double-blind placebo-controlled milk challenge and the third set of samples for immunological comparison.

The immunological markers are Immunoglobulins (E, G4, A), microbiota and basophilic activation. All patients are also evaluated for quality of life and nutritional status.

Eligibility criteria: Inclusion Criteria:

* Immunoglobulin E (IgE) milk \>0.1 kU/L
* Allergic reaction within 2 hours after intake of milk protein
* Age 5-15 years

Exclusion Criteria:

* Uncontrolled asthma, \>12 % increase in Forced Expiratory Volume in 1 second (FEV1) after inhaled bronchodilatator and Asthma Control Test (ACT)\<20
* No allergic reaction at a controlled milk challenge
* Cancer
* Severe immune deficiency
* Autoimmune disease
* Chronic urticaria
* Eosinophil esophagitis
* Pregnancy and breastfeeding
* Ongoing immunotherapy to one or more allergens

Primary outcomes:
measure: Number of participants that achieve tolerance to milk
timeFrame: 3.5 years after start of treatment
Secondary outcomes:
measure: Changes in level of basophil activation (CD sens) in blood
timeFrame: At baseline, after 6 months, after 3.5 years
measure: Changes in Quality Of Life: FAQLQ-PF
timeFrame: At baseline, after 3.5 years
measure: Changes in nutritional status
timeFrame: At baseline, after 3.5 years
measure: Frequency of treatment-demanding adverse effects
timeFrame: 3.5 years
measure: Changes in level of IgE milk in blood
timeFrame: Baseline, 6 months, 3.5 years
measure: Changes in level of IgG4 milk in blood
timeFrame: Baseline, 6 months, 3.5 years
measure: Changes in level of IgA in saliva
timeFrame: Baseline, 6 months, 3.5 years
measure: Changes in overall microbial composition in stools
timeFrame: Baseline, 6 months, 3.5 years
measure: Changes in overall microbial composition in saliva
timeFrame: Baseline, 6 months, 3.5 years
Other outcomes:
Locations:
city: Östersund
country: Sweden
facility: Solveig Röisgård
state: Jämtland Härjedalen
Study officials:
affiliation: Umeå University
name: Christina E West, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: