Milk Hypersensitivity
Conditions
Keywords
Food Allergy, Oral Immunotherapy, Immunoglobulin E
Brief summary
The purpose of this study is to determine if small oral doses of milk protein are safe and effective in decreasing sensitivity to cow's milk in allergic children.
Detailed description
This is a prospective, multi-center, clinical trial involving children aged 6 to 21 years with persistent cow's milk allergy. These children will be recruited from 2 sites (Johns Hopkins and Duke University) and will undergo initial screening and double-blind, placebo-controlled, food challenge (DBPCFC) to confirm threshold dose for reactivity to milk. Patients will be treated with milk oral immunotherapy (OIT) or placebo for 22-30 weeks. Those who reach an adequate maintenance dose for OIT will undergo a second DBPCFC. Those who develop desensitization will continue with daily milk intake and undergo a third DBPCFC. Those in the treatment group who are not desensitized will return to strict avoidance. Those in placebo group will be offered to begin treatment or continue with strict milk avoidance. Symptom and diet information will be collected initially and at regular intervals. Bloodwork, skin prick tests (SPTs), pulmonary function tests (PFTs), and oral secretion samples will be done initially and at periodic intervals.
Interventions
DRUGcow's milk powder
Milk powder given orally in escalating doses to a goal of 500 mg for approximately 23 weeks
OTHERPlacebo
Sponsors
Duke University
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Provide signed informed consent (by parent or legal guardian if the subject is a minor) and informed assent if applicable * Age 6 to 21 years * Must have history of symptomatic reactivity to cow's milk (eczema, urticaria, upper/lower resp., GI, other associated rash, oral symptoms) * History of positive skin prick test (wheal \>/= histamine control) or milk-Immunoglobulin E (IgE)\>0.35 kilounits per liter (kU/L) * Positive DBPCFC * All females of child bearing age must be using appropriate birth control
Exclusion criteria
* History of anaphylaxis requiring hospitalization * History of intubation related to asthma * Has the ability to tolerate \>2.4gram of milk protein at initial DBPCFC * Has a history of allergy to any component of vehicle * Pregnancy (need negative test) * Viral upper respiratory infection (URI) or gastroenteritis within 7days of OFC (OFC needs to be rescheduled) * Has pulmonary function tests \<80% of predicted (FEV1) or clinical history consistent with moderate persistent asthma * Currently taking greater than medium dose inhaled corticosteroid (\>400mcg/day fluticasone or fluticasone equivalent if \</=12yo or \>600mcg/day if \>12 years old) * Antihistamine within 1 week prior to skin testing or food challenges (Skin testing and/or food challenge needs to be rescheduled) * Systemic corticosteroid within 4 weeks prior to baseline visit * Receiving omalizumab, beta-blocker, Angiotensin-converting enzyme (ACE) inhibitor or tricyclic antidepressant therapy * Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes) * Participation in any interventional study for treatment of a food allergy in the past 12 months * Severe reaction at initial DBPCFC, defined as: i. Life-threatening anaphylaxis ii. Requires overnight hospitalization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Median Milk Threshold Dose Inducing a Reaction | Baseline and 23 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Cow Milk-IgE | Baseline and 23 weeks | IgE is measured in kilounits per liter (kU/L). Measurements were obtained at Baseline and at 23 weeks |
| Changes in Cow Milk Immunoglobulin G4 (IgG4) | Baseline and 23 weeks | IgG4 is measured in ug/mL. Measurements were obtained at Baseline and at 23 weeks |
Countries
United States
Participant flow
Recruitment details
Children between the ages of 6 and 21 years with a known history of IgE-mediated milk allergy were recruited from the pediatric allergy clinics at the Johns Hopkins University Hospital, Baltimore, Maryland, and Duke University Medical Center, Durham, North Carolina.
Pre-assignment details
Eligibility criteria were a positive skin prick test (SPT) response to milk extract (wheal ≥ histamine control) or milk immunoglobulin E (IgE) level of \> 0.35 kilounits per liter (kU/L) and a positive milk challenge result at baseline defined as reacting with clear signs, symptoms, or both to a cumulative dose of 2.5 g or less of milk protein.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Pre-measured doses of dry, nonfat powered milk prepared by the clinical research-registered dieticians
cow's milk powder: Milk powder given orally in escalating doses to a goal of 500 mg for approximately 23 weeks | 13 |
| Placebo Placebo | 7 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | persistent eczema during dose escalation | 1 | 0 |
Baseline characteristics
| Characteristic | Active Treatment | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13 Participants | 7 Participants | 20 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 | 9.3 years STANDARD_DEVIATION 3.3 | 10.2 years STANDARD_DEVIATION 3.3 | 9.5 years STANDARD_DEVIATION 2.6 |
| Current asthma | 9 Participants | 3 Participants | 12 Participants |
| Current eczema | 4 Participants | 2 Participants | 6 Participants |
| History of asthma | 12 Participants | 5 Participants | 17 Participants |
| History of eczema | 7 Participants | 4 Participants | 11 Participants |
| History of other food allergy | 10 Participants | 5 Participants | 15 Participants |
| Region of Enrollment United States | 13 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2,437 | 0 / 1,193 |
| other Total, other adverse events | 1,107 / 2,437 | 134 / 1,193 |
| serious Total, serious adverse events | 0 / 2,437 | 0 / 1,193 |
Outcome results
Primary
The Median Milk Threshold Dose Inducing a Reaction
Time frame: Baseline and 23 weeks
Population: One participant in the active treatment arm did not complete the study due to persistent eczema during dose escalation. The median milk threshold dose in both groups was 40 with a full range of 40-1340 at the baseline challenge.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active Treatment | The Median Milk Threshold Dose Inducing a Reaction | Baseline | 40 miligrams |
| Active Treatment | The Median Milk Threshold Dose Inducing a Reaction | Change at 23 weeks | 5100 miligrams |
| Placebo | The Median Milk Threshold Dose Inducing a Reaction | Baseline | 40 miligrams |
| Placebo | The Median Milk Threshold Dose Inducing a Reaction | Change at 23 weeks | 0 miligrams |
Secondary
Changes in Cow Milk-IgE
IgE is measured in kilounits per liter (kU/L). Measurements were obtained at Baseline and at 23 weeks
Time frame: Baseline and 23 weeks
Population: One participant in the active treatment arm did not complete the study due to persistent eczema during dose escalation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment | Changes in Cow Milk-IgE | 8 percentage of change |
| Placebo | Changes in Cow Milk-IgE | -5 percentage of change |
Secondary
Changes in Cow Milk Immunoglobulin G4 (IgG4)
IgG4 is measured in ug/mL. Measurements were obtained at Baseline and at 23 weeks
Time frame: Baseline and 23 weeks
Population: One participant in the active treatment arm did not complete the study due to persistent eczema during dose escalation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Treatment | Changes in Cow Milk Immunoglobulin G4 (IgG4) | 767 percentage of change |
| Placebo | Changes in Cow Milk Immunoglobulin G4 (IgG4) | 14 percentage of change |