Milk Hypersensitivity
Conditions
Keywords
Food hypersensitivity, Milk hypersensitivity, Milk allergy, Food allergy
Brief summary
Background and Rationale For patients with Immunoglobulin E (IgE)-mediated food allergy, the current management includes identification of the causative food and avoidance. Specifically, among young children, cow's milk allergy is the most common food allergy, occurring in as many as 2-3%. Given the prevalence of milk and the difficulty to avoid it in the diet, the investigators aim to investigate the safety and efficacy of oral immunotherapy for cow's milk allergy. Main Objective The primary objective is to study the efficacy of milk oral immunotherapy. Target Population Children aged six to 17 years with a history of cow's milk allergy will be recruited from The Children's Hospital of Philadelphia Allergy clinical offices for the investigators study.
Detailed description
Primary Study Interventions Prior to and after the desensitization, we will conduct double-blind placebo controlled food challenges to cow's milk protein. During the desensitization phase, we will give increasing doses of cow's milk protein by mouth on a weekly basis, as tolerated. The desensitization protocol starts with dilutional doses of milk and build up to a goal of 8 ounces of cow's milk. Main Study Outcome Measure The percentage of children completing the desensitization protocol in each study group will be the primary outcome measure.
Interventions
DRUGMilk Protein Powder
Milk protein powder will be administered in incremental doses during the desensitization protocol.
OTHERFood Challenge
DIETARY_SUPPLEMENTMilk Oral Immunotherapy
Subjects will participate in a desensitization protocol over the course of 13 weeks to reach a goal maintenance dose of 8 ounces of cow's milk. Once reaching maintenance, subjects will continue on this dose for 12 additional weeks.
Sponsors
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must be age six to 17 years and have a history of cow's milk allergy. Subjects shall maintain strict avoidance of consumption of all cow's milk protein containing foods. 2. Subjects will have a history (within the past six months) of a positive skin prick test to milk extract or an immunocap IgE level greater than 0.35 kilounits per liter (kU/L), and a positive allergic reaction history to milk within the past 12 months. 3. Subjects must be in good health, as determined by medical history and physical examination performed by a study physician. 4. Females of childbearing potential must be using an effective method of contraception, including abstinence, and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. 5. Informed consent of parent or legal guardian is required.
Exclusion criteria
1. Ability to tolerate eight ounces of cow's milk or eight grams of milk protein powder 2. Pregnancy 3. A history of soy allergy 4. A history of food protein induced enterocolitis syndrome to milk 5. A history of anaphylaxis requiring hospitalization 6. A history of intubation related to asthma and/or a history of an intensive care unit admission for asthma management 7. A current diagnosis of severe persistent asthma \[forced expiratory volume in 1 second (FEV1) \< 60% of predicted, as defined by National Heart, Lung, and Blood Institute (NHLBI) guidelines, despite current therapy 8. A current diagnosis of severe atopic dermatitis 9. A serious chronic medical condition, including neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease 10. Use of oral or injection steroids within one month of protocol initial visit 11. An acute illness within one week prior to the first dose of oral immunotherapy 12. Use of antihistamines within seven days prior to double blind placebo controlled food challenge (DBPCFC) 13. Use of chronic immunomodulatory therapy 14. Participation in another experimental therapy study 15. Participation in a study for the treatment of food allergy in the past 12 months 16. Inability to discontinue antihistamines for skin testing and food challenges
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Completed Desensitization Protocol | 1 year | Subjects who withdrew prior to completing the desensitization protocol and those who experienced anaphylaxis during the desensitization protocol (i.e., were unable to complete the protocol) were considered to be treatment failures. Subjects who completed the desensitization protocol were considered to be treatment successes. |
Countries
United States
Participant flow
Recruitment details
Children with a history of cow's milk allergy were referred from CHOP Allergy Clinics located in the main campus and satellite offices. Allergy and general pediatric practices in the greater Philadelphia area were also contacted by study staff as part of enrollment outreach.
Participants by arm
| Arm | Count |
|---|---|
| Delayed Sensitivity All subjects underwent a food challenge (week 2). Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 16 and continued thru Week 50. Total active participation lasted 51 weeks. | 8 |
| Immediate Sensitivity All subjects underwent a food challenge (week 2). Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 3 and continued thru Week 35. Total active participation lasted 38 weeks. | 17 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Immediate Sensitivity | Delayed Sensitivity | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 8 Participants | 25 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.88 years | 8.25 years | 8.68 years |
| Region of Enrollment United States | 17 participants | 8 participants | 25 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 4 / 17 |
| serious Total, serious adverse events | 2 / 8 | 1 / 17 |
Outcome results
Primary
Number of Subjects Who Completed Desensitization Protocol
Subjects who withdrew prior to completing the desensitization protocol and those who experienced anaphylaxis during the desensitization protocol (i.e., were unable to complete the protocol) were considered to be treatment failures. Subjects who completed the desensitization protocol were considered to be treatment successes.
Time frame: 1 year
Population: The analysis population included all subjects who began desensitization per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Delayed Sensitivity | Number of Subjects Who Completed Desensitization Protocol | 6 participants |
| Immediate Sensitivity | Number of Subjects Who Completed Desensitization Protocol | 12 participants |