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

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ClinicalTrials.gov Identifier: NCT00732654
Recruitment Status : Completed
First Posted : August 12, 2008
Results First Posted : May 15, 2017
Last Update Posted : May 15, 2017
Sponsor:
Collaborators:
Duke University
Greer Laboratories
Information provided by (Responsible Party):
Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Milk Allergy
Interventions Drug: Milk Protein Extract Immunotherapy goal of 4mg/day
Drug: Milk Protein Extract Immunotherapy goal of 7mg/day
Drug: Milk Powder Immunotherapy goal dose 2000 mg/day
Drug: Milk Powder Immunotherapy goal dose 1000mg/day
Enrollment 30
Recruitment Details  
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.
Arm/Group Title SLIT SLIT/OIT B SLIT/ OIT A
Hide Arm/Group Description

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.

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.

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.

Period Title: Overall Study
Started 10 10 10
Completed 10 9 10
Not Completed 0 1 0
Arm/Group Title OITA Group OITB Group SLIT Group Total
Hide Arm/Group Description

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.

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 10 10 10 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
<=18 years
10
 100.0%
10
 100.0%
10
 100.0%
30
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
Female
3
  30.0%
3
  30.0%
6
  60.0%
12
  40.0%
Male
7
  70.0%
7
  70.0%
4
  40.0%
18
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 10 participants 30 participants
10 10 10 30
History of anaphylaxis to Cow's Milk (CM)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
6
  60.0%
9
  90.0%
8
  80.0%
23
  76.7%
Other Food Allergies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
6
  60.0%
8
  80.0%
9
  90.0%
23
  76.7%
Asthma  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
9
  90.0%
9
  90.0%
8
  80.0%
26
  86.7%
Atopic Dermatitis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 10 participants 30 participants
6
  60.0%
6
  60.0%
10
 100.0%
22
  73.3%
1.Primary Outcome
Title Change in CM-specific Immunogloblin E (IgE)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not collected for one participant in the SLIT/OIT A group.
Arm/Group Title SLIT SLIT/OIT B SLIT/ OIT A
Hide Arm/Group Description:

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk Protein Extract Immunotherapy goal of 7mg/day: Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.

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 goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

Overall Number of Participants Analyzed 10 9 9
Median (Full Range)
Unit of Measure: kUa/L
0.8
(-390.0 to 10.0)
-13.5
(-170.8 to 471.7)
-9.4
(-49.1 to 42.1)
2.Primary Outcome
Title Change in CM-specific Immunoglobulin G4 (IgG4)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SLIT SLIT/OIT B SLIT/ OIT A
Hide Arm/Group Description:

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk Protein Extract Immunotherapy goal of 7mg/day: Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.

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 goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

Overall Number of Participants Analyzed 10 10 10
Median (Full Range)
Unit of Measure: kUa/L
9.9
(0.4 to 705.7)
157.2
(12.6 to 2415.7)
31.8
(-16.9 to 798.5)
3.Primary Outcome
Title Change in End Point Skin Test
Hide Description Allergen provoked skin test (mm)
Time Frame Change from baseline to after therapy (up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SLIT SLIT/OIT B SLIT/ OIT A
Hide Arm/Group Description:

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk Protein Extract Immunotherapy goal of 7mg/day: Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.

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 goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

Overall Number of Participants Analyzed 10 10 10
Median (Full Range)
Unit of Measure: mm
-3.1
(-6.1 to 2)
-3
(-10.9 to 2.3)
-2.5
(-5.1 to 0.9)
4.Primary Outcome
Title Oral Food Challenge Threshold (OFC) Threshold
Hide Description mg CM protein
Time Frame Change from baseline to after therapy (up to 18 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SLIT SLIT/OIT B SLIT/ OIT A
Hide Arm/Group Description:

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk Protein Extract Immunotherapy goal of 7mg/day: Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.

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 goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

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.

Milk Protein Extract Immunotherapy goal of 4mg/day: Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.

Milk 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.

Overall Number of Participants Analyzed 10 10 10
Median (Full Range)
Unit of Measure: mg
2458
(388.9 to 8139)
8089
(6138.9 to 8130)
7989
(4289 to 8129)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OITA Group OITB Group SLIT Group
Hide Arm/Group Description

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.

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.

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.

All-Cause Mortality
OITA Group OITB Group SLIT Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
OITA Group OITB Group SLIT Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)      0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
OITA Group OITB Group SLIT Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      10/10 (100.00%)      10/10 (100.00%)    
Gastrointestinal disorders       
Oropharyngeal inflammation *  10/10 (100.00%)  305 10/10 (100.00%)  840 10/10 (100.00%)  1164
*
Indicates events were collected by non-systematic assessment
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
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Corinne Keet
Organization: Johns Hopkins University
Phone: 4109555883
EMail: pediatricallergy@jhmi.edu
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00732654     History of Changes
Other Study ID Numbers: NA_00732654
First Submitted: August 8, 2008
First Posted: August 12, 2008
Results First Submitted: March 28, 2016
Results First Posted: May 15, 2017
Last Update Posted: May 15, 2017