Cow's Milk Protein SensitivityNCT01641731
Specific Oral Tolerance Induction in Children Allergic to Cow's Milk Proteins
A study testing Cow's milk in people with Cow's Milk Protein Sensitivity, run by Instituto de Investigación Hospital Universitario La Paz at 1 site in Spain.
Trial summary
Induction of oral tolerance in children allergic to cow's milk proteins is not risk-free. The analysis of factors that may influence the outcome is of utmost importance. The aim of the study is to analyse the efficacy and safety of the induction phase of oral tolerance induction according to specific IgE level, as… Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Cow's Milk Protein Sensitivity
- What is being tested?
- Cow's milk
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2009to Sep 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- -Patients diagnosed with cow's milk allergy meeting the following criteria: Immediate-type clinical manifestations, skin (urticaria, angioedema and/or erythema), digestive (acute vomiting and/or diarrhea) or respiratory (bronchospasm and/or rhinitis) involvement in the first two hours after cow's milk ingestion.
- Skin test readings ≥ 3 mm and specific IgE titers > 0.35 kU/l for whole cow's milk or someone of isolated CMPs (casein, alpha-lactalbumin, beta-lactoglobulin )
- Age 4 years old or older
- Specific IgE (measured by ImmunoCAP) lower than 50 KU/L for cow's milk or its proteins
- Positive oral food challenge with a dose higher than 2 mL
- Written informed consent signed by parents or legal representatives
Who cannot join
- Age younger than 4 y.o.
- Specific IgE higher than 50 kU/L
- Patients in whom oral food challenges is contraindicated, because of having a positive accidental reaction with moderate or severe symptoms in the previous 12 months prior to the inclusion.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Servicio de Alergia Infantil, Hospital Universitario La Paz
Madrid, 28046
About this study
Official title: Efficacy and Safety of Specific Oral Tolerance Induction in Children Allergic to Cow's Milk Proteins According to Their Serum Specific IgE Level
Induction of oral tolerance in children allergic to cow's milk proteins is not risk-free. The analysis of factors that may influence the outcome is of utmost importance.
The aim of the study is to analyse the efficacy and safety of the induction phase of oral tolerance induction according to specific IgE level, as well as adverse events during the maintenance phase.
Patients allergic to cow's milk are to be included in an oral tolerance induction protocol. Patients will be grouped according to specific IgE levels in serum (ImmunoCAP) into group I (sIgE<3.5 kU/L), II (sIgE 3.5-17 kU/L) and III (>17-50kU/L). Allergic children with similar characteristics will included as a control group. Visits are established at 1, 6 and 12 months after the induction phase. Serum specific IgE levels to cow's milk and its proteins will be determined at inclusion, and at 6 and 12 months visits after the induction phase.
Read the detailed description
Children allergic to cow's milk proteins (CMA) will be included. They have to be diagnosed with CMA during the first year of life and have attended periodic follow-up visits to our Allergy Clinic at Hospital La Paz (Madrid, Spain). Clinical data on personal history of asthma, allergy to other foods and positive reactions upon cow's milk ingestion along with their evolution from initial diagnosis will be recorded.
Prior to inclusion in the SOTI protocol, determination of serum specific IgE to cow's milk (CM), ALA, BLG and casein (ImmunoCAP, Phadia, Uppsala, Sweden) will be performed and current clinical status will be confirmed by oral food challenge (OFC) with cow's milk. An open OFC with CM (3 g of proteins per 100 mL) will be performed following a modified protocol according to the level of allergic sensitisation. Group I will start at a dose of 2 mL, and those in groups II and III started at a dose of 0.005 mL. In both protocols doses will be doubled until objective clinical reactivity is achieved.
Determination of serum specific IgE to cow's milk and its proteins will be performed in the follow-up at 6 and 12 months visits.
In order to evaluate the influence of the level of sensitisation in the result of SOTI, patients will be classified into three groups according to the level of sIgE for CM and/or its proteins: group I (0.35-3.5 kU/L, CAP Class I and II); group II (>3.5-17 kU/L, CAP Class III); group III (>17-50kU/L, CAP Class IV). The highest sIgE level against any of the CM or its proteins will determine the group of inclusion.
A control group of cow's milk allergic children, with similar levels of sIgE, will be included in order to evaluate the natural evolution to tolerance in CMA. They will be followed for one year, after which, clinical reactivity with OFC will be again confirmed. These control patients will selected among those who, after the initial OFC, refuse to undergo SOTI.
Specific Oral Tolerance Induction:
The initial dose for SOTI will be the previous dose that elicited symptoms in the OFC. Group I doses will be upped weekly in the hospital setting, and patients will maintain that dose twice daily at home. Groups II and III also will start with the previous dose that elicited symptoms in the OFC, but will receive incremental doses daily in the hospital setting until they reach a dose of 1 mL. Achieving an intake of 200 mL of milk (6 g of proteins) twice a day, which is the usual amount for patients of that age, will be considered complete tolerance.
Reactions occurring during the induction phase at the hospital will be treated according to the severity of symptoms. If patients present with mild non-objective symptoms, the same dose will be repeated. If the reaction is objective and limited to local symptoms, the previous dose will be given after the resolution of symptoms. If the reaction is generalised, involving two organ systems, SOTI will be continued with a dose which is two doses previous to the one that elicited symptoms. If the reaction involves three organ systems, the next dose administered will be reduced three steps in the dosage protocol. Written instructions will be given to parents regarding how to treat possible adverse reactions at home.
After the induction phase, patients will continue to consume 200 mL milk twice daily and dairy products were allowed freely.
In the maintenance phase, follow-up visits are scheduled at one month, six months and one year after finishing the induction phase. Data on tolerance of cow's milk and dairy products will be recorded. Adverse events upon ingestion will also be recorded.
- Conditions
- Cow's Milk Protein Sensitivity
- Being tested
- Cow's milk
- Keywords
- cow's milk protein allergy, oral tolerance induction
- Medical subject headings
- Milk Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cow's milkOther
Group I: Increase 2 mL until 10 mL, 10 mL until 50 mL, 20 mL until 100 mL and 50 mL until 200 mL was reached.
Groups II and III: Doubling dose until 1 mL, increase 2 mL until 20 mL, 5 mL until 50 mL, 10 mL until 100 mL and 20 mL until 200 mL was reached.
| Study group | Role | What they receive |
|---|---|---|
| Cow's milk | Active comparator | Not described Receives: Other: Cow's milk |
| Control group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerance to cow's milk
After administration of 250ml of milk, the patient is evaluated to determined if the milk is tolerated or not.
Measured: 12 months
Secondary outcomes (1)
Adverse events
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2012 (estimated)
- Study startMar 2009
- Primary completionMar 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cow's Milk Protein SensitivityStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Hospital Universitario La Paz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carmen García-Ara, MD, PhD, Principal investigator, Instituto de Investigación Sanitaria Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01641731
- Sponsor's protocol ID
- SOTI_CMA_HULP
- Status last verified
- Jul 2012
- First submitted
- 28 May 2012
- Last updated
- 17 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008 Feb;121(2):343-7. doi: 10.1016/j.jaci.2007.10.029. Epub 2007 Dec 26.
PubMed 18158176Zapatero L, Alonso E, Fuentes V, Martinez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008;18(5):389-96.
PubMed 18973104Caminiti L, Passalacqua G, Barberi S, Vita D, Barberio G, De Luca R, Pajno GB. A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy. Allergy Asthma Proc. 2009 Jul-Aug;30(4):443-8. doi: 10.2500/aap.2009.30.3221. Epub 2009 Mar 13.
PubMed 19288980Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007 Nov;62(11):1261-9. doi: 10.1111/j.1398-9995.2007.01501.x.
PubMed 17919140Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec;122(6):1154-60. doi: 10.1016/j.jaci.2008.09.030. Epub 2008 Oct 25.
PubMed 18951617Garcia-Ara C, Pedrosa M, Belver MT, Martin-Munoz MF, Quirce S, Boyano-Martinez T. Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level. Ann Allergy Asthma Immunol. 2013 Apr;110(4):290-4. doi: 10.1016/j.anai.2013.01.013. Epub 2013 Feb 14.
PubMed 23535095
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Specific Oral Tolerance Induction in Children Allergic to Cow's Milk Proteins According to Their Serum Specific IgE Level
- ClinicalTrials.gov ID
- NCT01641731
- Acronym / sponsor ID
- SOTI_CMA_HULP
- Conditions
- Cow's Milk Protein Sensitivity
- Keywords
- cow's milk protein allergy, oral tolerance induction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Instituto de Investigación Hospital Universitario La PazUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 17 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Induction of oral tolerance in children allergic to cow's milk proteins is not risk-free. The analysis of factors that may influence the outcome is of utmost importance.
The aim of the study is to analyse the efficacy and safety of the induction phase of oral tolerance induction according to specific IgE level, as well as adverse events during the maintenance phase.
Patients allergic to cow's milk are to be included in an oral tolerance induction protocol. Patients will be grouped according to specific IgE levels in serum (ImmunoCAP) into group I (sIgE<3.5 kU/L), II (sIgE 3.5-17 kU/L) and III (>17-50kU/L). Allergic children with similar characteristics will included as a control group. Visits are established at 1, 6 and 12 months after the induction phase. Serum specific IgE levels to cow's milk and its proteins will be determined at inclusion, and at 6 and 12 months visits after the induction phase.
Detailed description
Children allergic to cow's milk proteins (CMA) will be included. They have to be diagnosed with CMA during the first year of life and have attended periodic follow-up visits to our Allergy Clinic at Hospital La Paz (Madrid, Spain). Clinical data on personal history of asthma, allergy to other foods and positive reactions upon cow's milk ingestion along with their evolution from initial diagnosis will be recorded.
Prior to inclusion in the SOTI protocol, determination of serum specific IgE to cow's milk (CM), ALA, BLG and casein (ImmunoCAP, Phadia, Uppsala, Sweden) will be performed and current clinical status will be confirmed by oral food challenge (OFC) with cow's milk. An open OFC with CM (3 g of proteins per 100 mL) will be performed following a modified protocol according to the level of allergic sensitisation. Group I will start at a dose of 2 mL, and those in groups II and III started at a dose of 0.005 mL. In both protocols doses will be doubled until objective clinical reactivity is achieved.
Determination of serum specific IgE to cow's milk and its proteins will be performed in the follow-up at 6 and 12 months visits.
In order to evaluate the influence of the level of sensitisation in the result of SOTI, patients will be classified into three groups according to the level of sIgE for CM and/or its proteins: group I (0.35-3.5 kU/L, CAP Class I and II); group II (>3.5-17 kU/L, CAP Class III); group III (>17-50kU/L, CAP Class IV). The highest sIgE level against any of the CM or its proteins will determine the group of inclusion.
A control group of cow's milk allergic children, with similar levels of sIgE, will be included in order to evaluate the natural evolution to tolerance in CMA. They will be followed for one year, after which, clinical reactivity with OFC will be again confirmed. These control patients will selected among those who, after the initial OFC, refuse to undergo SOTI.
Specific Oral Tolerance Induction:
The initial dose for SOTI will be the previous dose that elicited symptoms in the OFC. Group I doses will be upped weekly in the hospital setting, and patients will maintain that dose twice daily at home. Groups II and III also will start with the previous dose that elicited symptoms in the OFC, but will receive incremental doses daily in the hospital setting until they reach a dose of 1 mL. Achieving an intake of 200 mL of milk (6 g of proteins) twice a day, which is the usual amount for patients of that age, will be considered complete tolerance.
Reactions occurring during the induction phase at the hospital will be treated according to the severity of symptoms. If patients present with mild non-objective symptoms, the same dose will be repeated. If the reaction is objective and limited to local symptoms, the previous dose will be given after the resolution of symptoms. If the reaction is generalised, involving two organ systems, SOTI will be continued with a dose which is two doses previous to the one that elicited symptoms. If the reaction involves three organ systems, the next dose administered will be reduced three steps in the dosage protocol. Written instructions will be given to parents regarding how to treat possible adverse reactions at home.
After the induction phase, patients will continue to consume 200 mL milk twice daily and dairy products were allowed freely.
In the maintenance phase, follow-up visits are scheduled at one month, six months and one year after finishing the induction phase. Data on tolerance of cow's milk and dairy products will be recorded. Adverse events upon ingestion will also be recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cow's milk | Active comparator | Other: Cow's milk |
| Control group | No intervention | – |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- -Patients diagnosed with cow's milk allergy meeting the following criteria: Immediate-type clinical manifestations, skin (urticaria, angioedema and/or erythema), digestive (acute vomiting and/or diarrhea) or respiratory (bronchospasm and/or rhinitis) involvement in the first two hours after cow's milk ingestion.
- Skin test readings ≥ 3 mm and specific IgE titers > 0.35 kU/l for whole cow's milk or someone of isolated CMPs (casein, alpha-lactalbumin, beta-lactoglobulin )
- Age 4 years old or older
- Specific IgE (measured by ImmunoCAP) lower than 50 KU/L for cow's milk or its proteins
- Positive oral food challenge with a dose higher than 2 mL
Key exclusion criteria (3 listed)
- Age younger than 4 y.o.
- Specific IgE higher than 50 kU/L
- Patients in whom oral food challenges is contraindicated, because of having a positive accidental reaction with moderate or severe symptoms in the previous 12 months prior to the inclusion.
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 |
|---|---|---|
| Cow's milkGroup I: Increase 2 mL until 10 mL, 10 mL until 50 mL, 20 mL until 100 mL and 50 mL until 200 mL was reached. Groups II and III: Doubling dose until 1 mL, increase 2 mL until 20 mL, 5 mL until 50 mL, 10 mL until 100 mL and 20 mL until 200 mL was reached. | Other | Cow's milk |
Primary outcome
Tolerance to cow's milk
Time frame: 12 months
After administration of 250ml of milk, the patient is evaluated to determined if the milk is tolerated or not.
1 secondary outcome
Adverse events
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2012.
- Background: PubMed 18158176Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008 Feb;121(2):343-7. doi: 10.1016/j.jaci.2007.10.029. Epub 2007 Dec 26.
- Background: PubMed 18973104Zapatero L, Alonso E, Fuentes V, Martinez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008;18(5):389-96.
- Background: PubMed 19288980Caminiti L, Passalacqua G, Barberi S, Vita D, Barberio G, De Luca R, Pajno GB. A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy. Allergy Asthma Proc. 2009 Jul-Aug;30(4):443-8. doi: 10.2500/aap.2009.30.3221. Epub 2009 Mar 13.
- Background: PubMed 17919140Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007 Nov;62(11):1261-9. doi: 10.1111/j.1398-9995.2007.01501.x.
- Background: PubMed 18951617Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec;122(6):1154-60. doi: 10.1016/j.jaci.2008.09.030. Epub 2008 Oct 25.
- Derived from this study: PubMed 23535095Garcia-Ara C, Pedrosa M, Belver MT, Martin-Munoz MF, Quirce S, Boyano-Martinez T. Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level. Ann Allergy Asthma Immunol. 2013 Apr;110(4):290-4. doi: 10.1016/j.anai.2013.01.013. Epub 2013 Feb 14.
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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.
Carmen García-Ara, MD, PhD principal investigator
Instituto de Investigación Sanitaria Hospital Universitario La Paz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cow's milk in people with Cow's Milk Protein Sensitivity, run by Instituto de Investigación Hospital Universitario La Paz at 1 site in Spain.
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 6 inclusion and 3 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 17 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Tolerance to cow's milk (time frame: 12 months). 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 NCT01641731, which also lists 6 linked publications.
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 17 Jul 2012.