Back to resultsMilk Desensitization in Children
Primary Purpose
Cow Milk Allergy
Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Oral Immunotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Cow Milk Allergy
Eligibility Criteria
Inclusion Criteria:
- 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).
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.
- Informed consent form signed by the parents or legal guardian
Exclusion Criteria:
- Patients with uncontrolled asthma or other uncontrolled respiratory diseases .
- Malignancies, autoimmune diseases and/or severe primary or secondary immune deficiencies.
- Patients receiving immunosuppressive therapy.
- Patients receiving β-blockers (including topical formulations).
- Associated diseases contraindicating the use of epinephrine: cardiovascular disease or severe hypertension.
Sites / Locations
- MUHC
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control
Treatment
Arm Description
Following randomization, this arm will receive no intervention. After twelve months, participants in this group will undergo a singe-blind, placebo-controlled oral food challenge
Following randomization, participants in this group will receive escalating doses milk, up to a daily dose of 200 ml. Once they attain that dose, they will maintain it for one month. At the end of this period, they will undergo a open challenge to 300 ml of milk. They will then enter a year-long follow-up period
Outcomes
Primary Outcome Measures
Presence or absence of allergic symptoms during an oral challenge to milk
Comparison of participants randomized to treatments arms who achieve milk desensitization compared to participants randomized to the control groups. This is measured by whether a participant is able to tolerate a total dose of 300 ml of milk during an oral food challenge
Secondary Outcome Measures
Change from baseline over the immunotherapy process of milk specigic IgE levels
Measurement of milk specigic IgE before, during and after the desensitization process
Change from baseline over the immunotherapy process of milk specigic IgA levels
Measurement of milk specigic IgA before, during and after the desensitization process
Change from baseline over the immunotherapy process of milk specigic IgG4 levels
Measurement of milk specigic IgG4 before, during and after the desensitization process
Change from baseline over the immunotherapy process of milk specigic IgE glycosylation levels
Measurement of milk specigic IgE glycosylation before, during and after the desensitization process
Change from baseline over the immunotherapy process of mast cell activation as measured by CD63 expression
Measurement of mast cell activation as measured by CD63 expression before, during and after the desensitization process
Change from baseline over the immunotherapy process of of DNA methylation levels
Measurement of DNA methylation levels before, during and after the desensitization proces
Change from baseline over the immunotherapy process of Regulatory T cell levels
Measurement of Regulatory T cell levels, before, during and after the desensitization process
Full Information
NCT ID
NCT03644381
First Posted
August 17, 2018
Last Updated
July 25, 2022
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
1. Study Identification
Unique Protocol Identification Number
NCT03644381
Brief Title
Milk Desensitization in Children
Official Title
Milk Desensitization and Induction of Tolerance in Children
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 3, 2013 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cow Milk Allergy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Description
Following randomization, this arm will receive no intervention. After twelve months, participants in this group will undergo a singe-blind, placebo-controlled oral food challenge
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Following randomization, participants in this group will receive escalating doses milk, up to a daily dose of 200 ml. Once they attain that dose, they will maintain it for one month. At the end of this period, they will undergo a open challenge to 300 ml of milk. They will then enter a year-long follow-up period
Intervention Type
Other
Intervention Name(s)
Oral Immunotherapy
Intervention Description
Starting from a very low level and over a period of several months, participants in the treatment group receive escalating doses of milk. Participants will also have blood and saliva draws to assess parameters of their immune system as well as skin prick testing
Primary Outcome Measure Information:
Title
Presence or absence of allergic symptoms during an oral challenge to milk
Description
Comparison of participants randomized to treatments arms who achieve milk desensitization compared to participants randomized to the control groups. This is measured by whether a participant is able to tolerate a total dose of 300 ml of milk during an oral food challenge
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change from baseline over the immunotherapy process of milk specigic IgE levels
Description
Measurement of milk specigic IgE before, during and after the desensitization process
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of milk specigic IgA levels
Description
Measurement of milk specigic IgA before, during and after the desensitization process
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of milk specigic IgG4 levels
Description
Measurement of milk specigic IgG4 before, during and after the desensitization process
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of milk specigic IgE glycosylation levels
Description
Measurement of milk specigic IgE glycosylation before, during and after the desensitization process
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of mast cell activation as measured by CD63 expression
Description
Measurement of mast cell activation as measured by CD63 expression before, during and after the desensitization process
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of of DNA methylation levels
Description
Measurement of DNA methylation levels before, during and after the desensitization proces
Time Frame
18 months
Title
Change from baseline over the immunotherapy process of Regulatory T cell levels
Description
Measurement of Regulatory T cell levels, before, during and after the desensitization process
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
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.
Informed consent form signed by the parents or legal guardian
Exclusion Criteria:
Patients with uncontrolled asthma or other uncontrolled respiratory diseases .
Malignancies, autoimmune diseases and/or severe primary or secondary immune deficiencies.
Patients receiving immunosuppressive therapy.
Patients receiving β-blockers (including topical formulations).
Associated diseases contraindicating the use of epinephrine: cardiovascular disease or severe hypertension.
Facility Information:
Facility Name
MUHC
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Milk Desensitization in Children
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