Growth, Safety and Tolerance of a Rice Protein Hydrolysate Formula in Infants With Cow's Milk Protein Allergy

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, controlled, randomized, prospective, non-inferiority, double blind intervention trial to evaluate the children growth (at 6, 9 and 12 months) using a rice hydrolysed protein formula compared to an extensively cow's milk protein hydrolysed formula for the management of Cow's Milk Protein Allergy (CMPA).

Detailed Description
-----------------
The main purpose of this study is to demonstrate that the rice protein hydrolysed based formula manufactured by Ordesa ensures proper growth and as secondary outcomes, that the formula is devoid of any risk of arsenic or other potential contaminants toxicity and its effect on the duration of CMA (Cow Milk Allergy) from cow's milk protein allergy.

Official Title
-----------------
Clinical Trial Evaluating the Effects on Growth, Safety and Tolerance of a Rice Protein Hydrolysate Formula Compared to a Cow's Milk Extensively Hydrolysed Protein Formula in Infants With Cow's Milk Protein Allergy

Conditions
-----------------
Cow's Milk Allergy

Intervention / Treatment
-----------------
* Other: HRF
* Other: eHF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects up to 10 months old with clinical history of a reaction to cow's milk protein and/or confirmed diagnosis (up to grade II anaphylaxis) of allergy to cow's milk protein by one of the following criteria, within two months prior to the baseline visit are eligible to enter the study: Negative or positive skin prick tests ( fresh milk, rice, casein hydrolysates) Negative or positive specific IgE for cow's milk proteins (alphalactalbumine, betalactoglobuline, caseine and cow's milk) Negative or positive Milk Atopy Patch Test Positive Double Blind Placebo Control Food Challenge (DBPCFC) with cow milk Gestational Age 37-42 weeks inclusive Apgar SCORE >7 at 5 minutes Singleton birth Birth weight ≥2.500 g Written informed consent Exclusion Criteria: Previous signs of allergy to any extensively hydrolysed formula Confirmed history of acute severe, potentially life threatening reaction after isolated accidental ingestion of cow's milk e.g. history of anaphylactic reaction, graded more or equal to grade III, as this could not be compatible with an allocation to the eHF group Daily formula intake < 100 ml Major congenital malformations or neonatal diseases Severe concurrent or chronic diseases Intrauterine growth retardation Neonatal infections ( e.g. CMV, HIV) Simultaneous participation in other clinical trials Parents not signing written informed consent Unable to adhere to protocol requirements or study visits due to non compliance of parents or caregivers. Liver, kidney, haematological abnormalities as judged clinically by investigators at baseline.

Ages Eligible for Study
-----------------
Maximum Age: 10 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRF (Rice formula)<br>Hydrolyzed Rice Protein Formula (HRF) | Other: HRF<br>* The subject will take the formula for a period of 12 months.<br>* Other names: HRF-2 from 6 months of age onwards;|
| Placebo Comparator: eHF (Extensive Hydrolysed Formula)<br>Extensive Hydrolysed Cow's Milk Protein Formula (eHF) | Other: eHF<br>* The subject will take the formula for a period of 12 months.<br>* Other names: eHF-2 from 6 months of age onwards;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growing change | To evaluate the children growth using a rice hydrolysed protein formula compared to an extensively cow's milk protein hydrolysed formula for the management of CMPA. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional adequacy | To monitor nutritional adequacy in terms of anthropometrics and proteic status. | 6 months | 
| Contaminants | To monitor the presence of possible contaminants in urine and hair samples coming from both infant formula groups (only in children exclusively or predominantly formula fed; ideally recruited from 0 to 6 months). Moreover the presence of possible contaminants will be evaluated also in powder formula and formula from baby bottles (only in 12 patients, randomly chosen). | 6 months | 
| Tolerance acquisition to cow's milk protein measured by a cow milk OFC (Open Food Challenge) | To evaluate the acquisition of tolerance between both groups. | 6 months |