Swedish Study of Immunotherapy for Milk Allergy in Children

Milk Allergy Clinical Trial

— SWITCH  

Official title:

Swedish Study of Immunotherapy for Milk Allergy in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03819556
• Other study ID #: F07
• Status: Recruiting
• Phase: N/A
• Start date: April 20, 2018
• Est. completion date: October 20, 2024

Study information

• Verified date: May 2020
• Source: Umeå University
• Contact: Christina West, Associated professor
• Phone: +46 703972792
• Email: christina.west[@]umu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: October 20, 2024
• Est. primary completion date: October 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Milk Allergy
• Milk Hypersensitivity

Intervention

Other:
• Milk protein in fresh milk
Milk protein in increasing doses.

Locations

Country	Name	City	State
Sweden	Solveig Röisgård	Östersund	Jämtland Härjedalen

Sponsors (1)

Lead Sponsor	Collaborator
Umeå University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants that achieve tolerance to milk	Tolerance is defined as absence of IgE-mediated allergic symptoms connected to a double-blind placebo-controlled milk challenge	3.5 years after start of treatment
Secondary	Changes in level of basophil activation (CD sens) in blood	Level of basophil activation at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins	At baseline, after 6 months, after 3.5 years
Secondary	Changes in Quality Of Life: FAQLQ-PF	Quality Of Life, reported by questionnaire (FAQLQ-PF) after completion of the intervention (3.5 years) compared to pre-trial baseline level. The scale used is Emotional Impact, Food Related anxiety and Dietary Limitations. Each question of the FAQLQ is answered on a 7-point scale. Total FAQLQ scores and domain scores are calculated by dividing the sum of completed items by the number of completed items. Total FaQLQ and domain scores range from 1 "no impairment" to 7 "maximal impairment". Higher values are a worse outcome (low health related quality of life). Subscale is Health related quality of life (HRQoL summary score=(Emotional Impact subscale score + Food Related anxiety subscale score+Dietary Limitations subscale score)/3.	At baseline, after 3.5 years
Secondary	Changes in nutritional status	Body Mass Index (BMI) after completion of the intervention (3.5 years) compared to pre-trial baseline levels	At baseline, after 3.5 years
Secondary	Frequency of treatment-demanding adverse effects	Number of events with adrenaline injection within 2 hours after a dose of milk (one or two injections) during step-up and maintenance therapy respectively. Number of events with inhalation of bronchodilatator within 2 hours after a dose of milk during step up and maintenance therapy respectively. Number of participants with two or more events with adrenaline injections during step-up and maintenance respectively. Number of participants with two or more events with inhalation of bronchodilatator during step-up and maintenance therapy respectively. Number of participants with no events of adrenaline injections. Number of participants with no events of inhalation with bronchodilatator.	3.5 years
Secondary	Changes in level of IgE milk in blood	Level of IgE milk including the components IgE casein, IgE lactoglobulin and lactalbumin at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins	Baseline, 6 months, 3.5 years
Secondary	Changes in level of IgG4 milk in blood	Level of IgG4 milk at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins	Baseline, 6 months, 3.5 years
Secondary	Changes in level of IgA in saliva	Level of IgA at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins	Baseline, 6 months, 3.5 years
Secondary	Changes in overall microbial composition in stools	The overall microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing	Baseline, 6 months, 3.5 years
Secondary	Changes in overall microbial composition in saliva	The microbial composition at baseline, after dose escalation and after maintenance therapy and one additional week free from milk proteins will be assessed using amplicon sequencing	Baseline, 6 months, 3.5 years