Clinical trial NCT03644381: Milk Desensitization in Children
Official title: Milk Desensitization and Induction of Tolerance in Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cow Milk Allergy
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2018-08-23
Enrollment: 84
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will assess a novel and potentially life-changing therapy, by actively treating Cow's Milk Allergy (CMA) using Oral Immunotherapy, which may allow patients to safely consume milk and other dairy products.

Detailed description: This is a randomized control study with a cross-over design. Eighty four boys and girls with between 6 to 20 years of age, diagnosed with IgE-mediated cow's milk allergy using strict skin testing and serological criteria, will be recruited for this study. 42 will undergo oral immunotherapy, while 42 will be followed as natural history controls but will be offered similar therapy, should it be successful, at the completion of one year. OIT subjects will initaiate therapy with a 2-day rush desensitization treatment using oral doses of milk, in the investigator's Clinical Investigation Unit. They will then continue the highest tolerated dose of milk at home for two weeks. Subsequently, they will return for weekly increases in doses until a maximum of 200 ml of milk is ingested daily. The primary clinical outcome will be a comparison of the amount of milk consumed safely on oral challenge performed prior to OIT, when the OIT dose has reached its maximum (200 ml or highest tolerated dose) and after one year of therapy. Patients will also be followed with clinical symptom scores and adverse event diarie. Their immunological parameters such as changes in milk-specific IgE, blocking antibodies (IgG4 and IgA) and regulatory T and B cells will also be monitored. It is expected that there will be important improvement in the ability to safely ingest milk and other dairy products, and this will be accompanied by significant decreases in IgE and increases in Regulatory T and B cells.

Eligibility criteria: Inclusion Criteria:

1. A history suggestive of IgE-mediated allergy to milk. An IgE-mediated reaction to a specific food is defined as a minimum of 2 mild symptoms and/or 1 moderate and/or 1 severe symptom that began within 1-20 minutes after ingestion or contact. Mild IgE-mediated symptoms include: pruritus, urticaria, flushing, or rhinoconjunctivitis. Moderate symptoms include angioedema (of face or lips), throat tightness, gastrointestinal complaints (vomiting, cramping, pain and/or diarrhea), or airway involvement (cough, nasal blockage, mucous ); severe symptoms include bronchospasm, wheezing, hypoxia, cyanosis, low blood pressure, or circulatory collapse (shock) (appendix A ,table 1) (61).
2. The presence of at least one of the following confirmatory tests:

   * (a) Positive skin prick test to milk (weal diameter 3 mm larger than that of the normal saline control). The allergen used will be commercially available milk extracts (Omega Labs, Montreal, QC). Skin tests will traced in ink, tape transferred to paper and wheal diameter measured by computer assisted planometry.
   * (b) Detection of serum specific IgE (\>0.35 kU/L) to milk or any of its proteins, measured by fluorescence enzyme immunoassay (Immunocap, Phadia, Uppsala, Sweden). The range for Immuncap is 0.35 - 100 and changes over time can be monitored effectively.
3. Informed consent form signed by the parents or legal guardian

Exclusion Criteria:

1. Patients with uncontrolled asthma or other uncontrolled respiratory diseases .
2. Malignancies, autoimmune diseases and/or severe primary or secondary immune deficiencies.
3. Patients receiving immunosuppressive therapy.
4. Patients receiving β-blockers (including topical formulations).
5. Associated diseases contraindicating the use of epinephrine: cardiovascular disease or severe hypertension.

Primary outcomes:
measure: Presence or absence of allergic symptoms during an oral challenge to milk
timeFrame: 12 months
Secondary outcomes:
measure: Change from baseline over the immunotherapy process of milk specigic IgE levels
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of milk specigic IgA levels
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of milk specigic IgG4 levels
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of milk specigic IgE glycosylation levels
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of mast cell activation as measured by CD63 expression
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of of DNA methylation levels
timeFrame: 18 months
measure: Change from baseline over the immunotherapy process of Regulatory T cell levels
timeFrame: 18 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: MUHC
state: Quebec
Study officials:
References: