Milk Allergy
Conditions
Keywords
Food Allergy, Oral Immunotherapy, Immunoglobulin E
Brief summary
The purpose of this study is to determine if small oral and sublingual doses of milk protein are safe and effective in decreasing sensitivity to cow's milk in allergic children.
Interventions
DRUGMilk Protein Extract Immunotherapy goal of 4mg/day
Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.
DRUGMilk Protein Extract Immunotherapy goal of 7mg/day
Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.
DRUGMilk Powder Immunotherapy goal dose 2000 mg/day
Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.
DRUGMilk Powder Immunotherapy goal dose 1000mg/day
Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.
Sponsors
Duke University
Greer Laboratories
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Are age 6 to 21 years * Provide signed informed consent (by parent or legal guardian if the subject is a minor), and informed assent if applicable * Have a history of symptomatic reactivity to cow's milk (i.e. Eczema, urticaria, upper or lower respiratory symptoms, GI disturbances, other rash or oral symptoms) * Have a positive skin prick test (defined as wheal 3 mm ≥ negative control) and cow's milk- immunoglobulin E (IgE) \> 0.35 kilo Immunoglobulin Units (kIU)/L * Have a positive OFC to cow's milk at a cumulative dose of less than 184 milligrams of cow's milk intact protein (2,400 mg total milk protein). * Are using appropriate birth control if subject is female and of child bearing age. * Have self-injectable epinephrine (ie. EpiPen® or EpiPen Jr.®) available at home
Exclusion criteria
* Have a history of severe anaphylaxis defined as hypoxia (cyanosis or SpO2 ≤ 92% at any stage), hypotension, confusion, collapse, loss of consciousness; or incontinence * Have a history of intubation related to asthma * Tolerate more than 184 milligrams of intact cow's milk protein at initial OFC * Are pregnant or lactating * Have a viral Upper Respiratory Infection (URI) or gastroenteritis within 7 days of OFC (OFC needs to be rescheduled) * Have pulmonary function tests \<80% of predicted (FEV1) or clinical history consistent with more than moderate persistent asthma * Are currently taking greater than medium dose inhaled corticosteroid (\>400 mcg/day fluticasone or fluticasone equivalent if ≤ 12 years old or \> 600 mcg/day if \> 12 years old) * Are unable to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or food challenges * Have used systemic corticosteroids within 4 weeks prior to baseline visit * Are receiving omalizumab, beta-blocker, Angiotensin Converting Enzyome (ACE) inhibitor or tricyclic antidepressant therapy * Have a chronic disease (other than asthma, atopic dermatitis or rhinitis) requiring therapy (e.g., heart disease, diabetes) * Have participated in any interventional study for treatment of a food allergy in the past 12 months * Have a severe reaction at initial DBPCFC, defined as either: Life-threatening anaphylaxis, or Reaction requiring hospitalization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CM-specific Immunogloblin E (IgE) | Change from baseline to after therapy (up to 18 months) | Cow's milk specific IgE was measured at baseline and after therapy (kUa/L) |
| Change in CM-specific Immunoglobulin G4 (IgG4) | Change from baseline to after therapy (up to 18 months) | Cow's milk specific IgG4 was measured at baseline and after therapy (kUa/L) |
| Change in End Point Skin Test | Change from baseline to after therapy (up to 18 months) | Allergen provoked skin test (mm) |
| Oral Food Challenge Threshold (OFC) Threshold | Change from baseline to after therapy (up to 18 months) | mg CM protein |
Countries
United States
Participant flow
Pre-assignment details
33 patients underwent screening Double-Blinded Placebo-Controlled Food Challenges (DBPCFCs). Two subjects failed screening because they tolerated at least 2.5g at the initial DBPCFC. One subject declined to continue in the study after the food challenge. 30 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| OITA Group These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 2000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year.
Milk Powder Immunotherapy : Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.
Milk Protein Extract Immunotherapy : Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. | 10 |
| OITB Group These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 1000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year.
Milk Powder Immunotherapy : Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.
Milk Protein Extract Immunotherapy : Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. | 10 |
| SLIT Group These subjects will have a dose escalation of the milk protein extract given sublingually. After dose escalation, they will continue on the sublingual daily maintenance dose for approximately one year.
Milk Protein Extract Immunotherapy : Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | OITA Group | OITB Group | SLIT Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Asthma | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Atopic Dermatitis | 6 Participants | 6 Participants | 10 Participants | 22 Participants |
| History of anaphylaxis to Cow's Milk (CM) | 6 Participants | 9 Participants | 8 Participants | 23 Participants |
| Other Food Allergies | 6 Participants | 8 Participants | 9 Participants | 23 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 10 participants | 30 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Change in CM-specific Immunogloblin E (IgE)
Cow's milk specific IgE was measured at baseline and after therapy (kUa/L)
Time frame: Change from baseline to after therapy (up to 18 months)
Population: Data was not collected for one participant in the SLIT/OIT A group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SLIT | Change in CM-specific Immunogloblin E (IgE) | 0.8 kUa/L |
| SLIT/OIT B | Change in CM-specific Immunogloblin E (IgE) | -13.5 kUa/L |
| SLIT/ OIT A | Change in CM-specific Immunogloblin E (IgE) | -9.4 kUa/L |
Primary
Change in CM-specific Immunoglobulin G4 (IgG4)
Cow's milk specific IgG4 was measured at baseline and after therapy (kUa/L)
Time frame: Change from baseline to after therapy (up to 18 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SLIT | Change in CM-specific Immunoglobulin G4 (IgG4) | 9.9 kUa/L |
| SLIT/OIT B | Change in CM-specific Immunoglobulin G4 (IgG4) | 157.2 kUa/L |
| SLIT/ OIT A | Change in CM-specific Immunoglobulin G4 (IgG4) | 31.8 kUa/L |
Primary
Change in End Point Skin Test
Allergen provoked skin test (mm)
Time frame: Change from baseline to after therapy (up to 18 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SLIT | Change in End Point Skin Test | -3.1 mm |
| SLIT/OIT B | Change in End Point Skin Test | -3 mm |
| SLIT/ OIT A | Change in End Point Skin Test | -2.5 mm |
Primary
Oral Food Challenge Threshold (OFC) Threshold
mg CM protein
Time frame: Change from baseline to after therapy (up to 18 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SLIT | Oral Food Challenge Threshold (OFC) Threshold | 2458 mg |
| SLIT/OIT B | Oral Food Challenge Threshold (OFC) Threshold | 8089 mg |
| SLIT/ OIT A | Oral Food Challenge Threshold (OFC) Threshold | 7989 mg |