CompletedNCT00732654Updated May 15, 2017Results posted

The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy

A Phase 1/2 interventional study of Milk Protein Extract Immunotherapy goal of 4mg/day and Milk Protein Extract Immunotherapy goal of 7mg/day in Milk Allergy, sponsored by Johns Hopkins University. Completed at 2 sites in United States. Open to participants aged 6 Years to 21 Years. Per ClinicalTrials.gov, last updated 2017-05-15.

Sponsored by Johns Hopkins University · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 30
Allocation: Randomized
Ages: 6 Years to 21 Years
Sex: All

Study 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.

Conditions studied

Milk Allergy

Browse trials for

Keywords

Food Allergy
Oral Immunotherapy
Immunoglobulin E

In context

Hypersensitivity

1,916 studies on the registry are indexed under Hypersensitivity; 265 are open to participants now.

This study's enrollment of 30 is below the median of 57 across 1,384 interventional studies indexed under Hypersensitivity.

Browse Hypersensitivity studies →

Lead sponsor

Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.

Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 6 Years to 21 Years
Sexes eligible: All
Accepts 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

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 30 participants (actual)

Study arms

Experimental
Sublingual Immunotherapy (SLIT)
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.
Drug: Milk Protein Extract Immunotherapy goal of 4mg/day · Drug: Milk Protein Extract Immunotherapy goal of 7mg/day
Experimental
SLIT/ Oral Immunotherpay (OIT) B
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.
Drug: Milk Protein Extract Immunotherapy goal of 4mg/day · Drug: Milk Powder Immunotherapy goal dose 1000mg/day
Experimental
SLIT/ OIT A
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.
Drug: Milk Protein Extract Immunotherapy goal of 4mg/day · Drug: Milk Powder Immunotherapy goal dose 2000 mg/day

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.

What researchers measure

Primary outcomes

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)
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)
Change in End Point Skin Test
Allergen provoked skin test (mm)
Time frame: Change from baseline to after therapy (up to 18 months)
Oral Food Challenge Threshold (OFC) Threshold
mg CM protein
Time frame: Change from baseline to after therapy (up to 18 months)

Results

Posted May 15, 2017

Limitations and caveats

Please refer to the links section, it contains a link to the publication of this research study in the Journal of Allergy and Clinical Immunology

Participant flow

Participant flow — Overall Study
Milestone	SLIT	SLIT/OIT B	SLIT/ OIT A
Started	10	10	10
Completed	10	9	10
Not completed	0	1	0

Outcome measures

PrimaryChange 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)
Reported as:: Median · kUa/L

Change in CM-specific Immunogloblin E (IgE)
kUa/L	SLIT	SLIT/OIT B	SLIT/ OIT A
Change in CM-specific Immunogloblin E (IgE)	0.8 (-390.0 to 10.0)	-13.5 (-170.8 to 471.7)	-9.4 (-49.1 to 42.1)

PrimaryChange 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)
Reported as:: Median · kUa/L

Change in CM-specific Immunoglobulin G4 (IgG4)
kUa/L	SLIT	SLIT/OIT B	SLIT/ OIT A
Change in CM-specific Immunoglobulin G4 (IgG4)	9.9 (0.4 to 705.7)	157.2 (12.6 to 2415.7)	31.8 (-16.9 to 798.5)

PrimaryChange in End Point Skin Test

Allergen provoked skin test (mm)

Time frame:: Change from baseline to after therapy (up to 18 months)
Reported as:: Median · mm

Change in End Point Skin Test
mm	SLIT	SLIT/OIT B	SLIT/ OIT A
Change in End Point Skin Test	-3.1 (-6.1 to 2)	-3 (-10.9 to 2.3)	-2.5 (-5.1 to 0.9)

PrimaryOral Food Challenge Threshold (OFC) Threshold

mg CM protein

Time frame:: Change from baseline to after therapy (up to 18 months)
Reported as:: Median · mg

Oral Food Challenge Threshold (OFC) Threshold
mg	SLIT	SLIT/OIT B	SLIT/ OIT A
Oral Food Challenge Threshold (OFC) Threshold	2458 (388.9 to 8139)	8089 (6138.9 to 8130)	7989 (4289 to 8129)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
OITA Group	—	0/10 (0%)	10/10 (100%)
OITB Group	—	0/10 (0%)	10/10 (100%)
SLIT Group	—	0/10 (0%)	10/10 (100%)

Most frequent other events

Most frequent other events
Event	OITA Group	OITB Group	SLIT Group
Oropharyngeal inflammationGastrointestinal disorders	10/10	10/10	10/10

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	OITA Group	OITB Group	SLIT Group	Total
<=18 years	10	10	10	30
Between 18 and 65 years	0	0	0	0
>=65 years	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	OITA Group	OITB Group	SLIT Group	Total
Female	3	3	6	12
Male	7	7	4	18

Region of Enrollment
Region of Enrollment(participants)	OITA Group	OITB Group	SLIT Group	Total
United States	10	10	10	30

History of anaphylaxis to Cow's Milk (CM)
History of anaphylaxis to Cow's Milk (CM)(Participants)	OITA Group	OITB Group	SLIT Group	Total
Count of participants	6	9	8	23

Other Food Allergies
Other Food Allergies(Participants)	OITA Group	OITB Group	SLIT Group	Total
Count of participants	6	8	9	23

Asthma
Asthma(Participants)	OITA Group	OITB Group	SLIT Group	Total
Count of participants	9	9	8	26

Atopic Dermatitis
Atopic Dermatitis(Participants)	OITA Group	OITB Group	SLIT Group	Total
Count of participants	6	6	10	22

Study locations

2 sites

Johns Hopkins Hospital
Baltimore, Maryland 21287, United States
Duke University
Durham, North Carolina 27710, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00732654
Lead sponsor: Johns Hopkins University
Collaborators: Duke University, Greer Laboratories
Responsible party: Sponsor
First posted: Aug 12, 2008
Start date: Aug 2008
Primary completion: Jun 2010
Completion: Jun 2012
Results posted: May 15, 2017
Last update: May 15, 2017

Study contacts

Robert Wood, MD

principal investigator · Johns Hopkins University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Hypersensitivity→

Other studies from this sponsor

Johns Hopkins University

Start the discussion