Milk Desensitization in Children

NCT ID: NCT03644381

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-03
• Study Completion Date: 2025-06-30

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.

Conditions

Cow Milk Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Treatment

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

Group Type: EXPERIMENTAL

Oral Immunotherapy

Intervention Type: OTHER

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

Interventions

Oral Immunotherapy

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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Bruce Mazer

Executive Director and CSO (Interim)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

MUHC

Montreal, Quebec, Canada

Countries

Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

MP-CUSM-12-090-PED

Identifier Type: -

Identifier Source: org_study_id