Milk AllergyPhase 1/2NCT00732654

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

A Phase 1/2 study testing Milk Protein Extract Immunotherapy goal of 4mg/day, Milk Protein Extract Immunotherapy goal of 7mg/day and Milk Powder Immunotherapy goal dose 2000 mg/day in people with Milk Allergy, run by Johns Hopkins University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 6 to 21 years
Conditions the study is for: Milk Allergy
What is being tested?: Milk Protein Extract Immunotherapy goal of 4mg/day, Milk Protein Extract Immunotherapy goal of 7mg/day and Milk Powder Immunotherapy goal dose 2000 mg/day
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 2 sitesUnited States
Study dates: Aug 2008to Jun 2012
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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

Show all 14Show fewer

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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

Other trials in United States

About this study

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: Milk Allergy
Being tested: Milk Protein Extract Immunotherapy goal of 4mg/day, Milk Protein Extract Immunotherapy goal of 7mg/day, Milk Powder Immunotherapy goal dose 2000 mg/day, Milk Powder Immunotherapy goal dose 1000mg/day
Keywords: Food Allergy, Oral Immunotherapy, Immunoglobulin E
Medical subject headings: Milk Hypersensitivity, Food Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Milk Protein Extract Immunotherapy goal of 4mg/dayDrug
Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.
Milk Protein Extract Immunotherapy goal of 7mg/dayDrug
Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.
Milk Powder Immunotherapy goal dose 2000 mg/dayDrug
Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.
Milk Powder Immunotherapy goal dose 1000mg/dayDrug
Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.

Study groups in NCT00732654
Study group	Role	What they receive
Sublingual Immunotherapy (SLIT)	Experimental	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. Receives: Drug: Milk Protein Extract Immunotherapy goal of 4mg/day; Drug: Milk Protein Extract Immunotherapy goal of 7mg/day
SLIT/ Oral Immunotherpay (OIT) B	Experimental	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. Receives: Drug: Milk Protein Extract Immunotherapy goal of 4mg/day; Drug: Milk Powder Immunotherapy goal dose 1000mg/day
SLIT/ OIT A	Experimental	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. Receives: Drug: Milk Protein Extract Immunotherapy goal of 4mg/day; Drug: Milk Powder Immunotherapy goal dose 2000 mg/day

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in CM-specific Immunogloblin E (IgE)
Cow's milk specific IgE was measured at baseline and after therapy (kUa/L)
Measured: 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)
Measured: Change from baseline to after therapy (up to 18 months)
Change in End Point Skin Test
Allergen provoked skin test (mm)
Measured: Change from baseline to after therapy (up to 18 months)
Oral Food Challenge Threshold (OFC) Threshold
mg CM protein
Measured: Change from baseline to after therapy (up to 18 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2008Jun 2012

First posted12 Aug 2008 (estimated)
Study startAug 2008
Primary completionJun 2010
Study completionJun 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Milk AllergyStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00732654
Sponsor's protocol ID: NA_00732654
Status last verified: Apr 2017
First submitted: 8 Aug 2008
Last updated: 15 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
Phase 2b Study of RPT904 as Monotherapy in Participants With IgE-Mediated Food Allergy
Immune System Diseases, Ig-E Mediated Food Allergy
Recruiting
Evaluation of the Tolerance of a New Formula Based on Hydrolyzed Rice Proteins in Children With Cow's Milk Allergy
IgE-Mediated Cow Milk Allergy
Not yet recruiting
Performance of the Basophil Activation Test in the Diagnosis of IgE-mediated Cow's Milk Allergy in Infants and Evaluation of Hydrolysate Allergenicity.
Milk Allergy
Recruiting
Infant Formula in Infants and Children With Cow's Milk Allergy
Cow's Milk Allergy
RecruitingPhase 3
A 52-week Study of Remibrutinib in IgE-mediated Food Allergy
IgE-Mediated Food Allergy, Peanut Allergy

All Milk Allergy trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy
ClinicalTrials.gov ID: NCT00732654
Acronym / sponsor ID: NA_00732654
Conditions: Milk Allergy
Keywords: Food Allergy, Oral Immunotherapy, Immunoglobulin E
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: Duke University, Greer Laboratories
Study start: Aug 2008
Primary completion: Jun 2010 (actual)
Study completion: Jun 2012 (actual)
First posted: 12 Aug 2008 (estimated)
Results: Posted 15 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

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

Who may qualify

Ages: 6 to 21 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

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).

Key exclusion criteria (14 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Milk Protein Extract Immunotherapy goal of 4mg/daySublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.	Drug	SLIT/ OIT A, SLIT/ Oral Immunotherpay (OIT) B, Sublingual Immunotherapy (SLIT)
Milk Protein Extract Immunotherapy goal of 7mg/daySublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.	Drug	Sublingual Immunotherapy (SLIT)
Milk Powder Immunotherapy goal dose 2000 mg/dayMilk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.	Drug	SLIT/ OIT A
Milk Powder Immunotherapy goal dose 1000mg/dayMilk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.	Drug	SLIT/ Oral Immunotherpay (OIT) B

Primary outcome

Change in CM-specific Immunogloblin E (IgE)
Time frame: 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)
Time frame: 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
Time frame: Change from baseline to after therapy (up to 18 months)
Allergen provoked skin test (mm)
Oral Food Challenge Threshold (OFC) Threshold
Time frame: Change from baseline to after therapy (up to 18 months)
mg CM protein

Results and safety

Results posted to the registry on 15 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SLIT	10	10
SLIT/OIT B	10	9
SLIT/ OIT A	10	10

Primary outcome: Change in CM-specific Immunogloblin E (IgE)

Time frame: Change from baseline to after therapy (up to 18 months). Median (Full Range). Unit: kUa/L

Measure	SLIT n = 10	SLIT/OIT B n = 9	SLIT/ OIT A n = 9
Value	0.8 (-390.0 to 10.0)	-13.5 (-170.8 to 471.7)	-9.4 (-49.1 to 42.1)

Population analysed: Data was not collected for one participant in the SLIT/OIT A group.

Primary outcome: Change in CM-specific Immunoglobulin G4 (IgG4)

Time frame: Change from baseline to after therapy (up to 18 months). Median (Full Range). Unit: kUa/L

Measure	SLIT n = 10	SLIT/OIT B n = 10	SLIT/ OIT A n = 10
Value	9.9 (0.4 to 705.7)	157.2 (12.6 to 2415.7)	31.8 (-16.9 to 798.5)

Primary outcome: Change in End Point Skin Test

Time frame: Change from baseline to after therapy (up to 18 months). Median (Full Range). Unit: mm

Measure	SLIT n = 10	SLIT/OIT B n = 10	SLIT/ OIT A n = 10
Value	-3.1 (-6.1 to 2)	-3 (-10.9 to 2.3)	-2.5 (-5.1 to 0.9)

Primary outcome: Oral Food Challenge Threshold (OFC) Threshold

Time frame: Change from baseline to after therapy (up to 18 months). Median (Full Range). Unit: mg

Measure	SLIT n = 10	SLIT/OIT B n = 10	SLIT/ OIT A n = 10
Value	2458 (388.9 to 8139)	8089 (6138.9 to 8130)	7989 (4289 to 8129)

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OITA Group	0 of 10 (0%)	10 of 10 (100%)	Not reported
OITB Group	0 of 10 (0%)	10 of 10 (100%)	Not reported
SLIT Group	0 of 10 (0%)	10 of 10 (100%)	Not reported

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Milk Allergy

Active, not recruitingPhase 2
Phase 2b Study of RPT904 as Monotherapy in Participants With IgE-Mediated Food Allergy
Immune System Diseases, Ig-E Mediated Food Allergy
Recruiting
Evaluation of the Tolerance of a New Formula Based on Hydrolyzed Rice Proteins in Children With Cow's Milk Allergy
IgE-Mediated Cow Milk Allergy
Not yet recruiting
Performance of the Basophil Activation Test in the Diagnosis of IgE-mediated Cow's Milk Allergy in Infants and Evaluation of Hydrolysate Allergenicity.
Milk Allergy
Recruiting
Infant Formula in Infants and Children With Cow's Milk Allergy
Cow's Milk Allergy
RecruitingPhase 3
A 52-week Study of Remibrutinib in IgE-mediated Food Allergy
IgE-Mediated Food Allergy, Peanut Allergy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert Wood, MD principal investigator

Johns Hopkins University

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in CM-specific Immunogloblin E (IgE) (time frame: Change from baseline to after therapy (up to 18 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00732654.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.