Whole Grain, Gluten-containing Cereal and PROBIOtics to Evaluate Digestive TOLERAance and Immuno-inflammatory Response

Study Overview
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Brief Summary
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This study will assess the development of gastrointestinal health in terms of digestive tolerability and immune-inflammatory response at the intestinal level comparing a conventional gluten-free cereal with a new cereal with prebiotics, probiotics and a very moderate amount of gluten. These are products adapted to infant feeding since 4 Months.

Detailed Description
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In 2008 the ESPGHAN recommended not to give gluten cereals before 4 months but not after 7 months. Although the introduction of gluten in this window was linked to a posible preventive effect on celiac disease, the truth is that it has not been demonstrated. In any case, high exposures to gluten since the 4 months have been associated with a higher incidence of celiac disease and current recommendations propose moderate and progressive exposure to gluten between 4 and 6 months old.

Official Title
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Study of the Initiation of Complementary Feeding With a Whole Grain, Gluten-containing Infant Cereal and PROBIOtics to Evaluate Digestive TOLERAance and Immuno-inflammatory Response at the Intestinal Level.

Conditions
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Gastrointestinal Disorder, Immunologic Diseases in Children

Intervention / Treatment
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* Dietary Supplement: Experimental cereal
* Dietary Supplement: Conventional cereal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy term infants (>37 weeks) vaginal delivery Adequate birth weight for gestational age (10-90 percentile) Infants with normal growth curve (10-90 percentile) Infants who were breastfeeding for at least 4 weeks, and at least half of the takes have been by breastfeeding. Infants aged 4 months (+/- 1 week) at the time of study inclusion no longer following breastfeeding, or mixed breastfeeding and if they are breast-feeding, no more than one shot a day. Availability to continue throughout the study period. Signature of informed consent by partents/guardians. Exclusion Criteria: Infants who were born by cesarean section Infants born from preconception obese mothers Infants born from diabetic mothers or mothers with gestational diabetes Infants with a family history of celiac disease (parents or siblings) Infants who have had or have some type of allergic manifestation or allergic pathology Infants who have needed antibiotic treatment or have received some type of probiotic (the week before inclusion) Infants with malformations, diseases or conditions and physical disabilities that cause changes in growth and/or nutritional status Infants diagnosed with any immune system-related disease (primary immunodeficiency) Infants with a known allergy and/or intolerance to cow's milk protein Parents' inability to follow study (at the discretion of the researcher)

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Cereal<br>Experimental cereal with probiotics, prebiotic fiber and low carbohydrates through all the duration of the study. | Dietary Supplement: Experimental cereal<br>* Cereal containing probiotics, prebiotic fiber and low carbohydrates<br>|
| Active Comparator: Conventional cereal<br>Conventional gluten free cereal between 4 and 6 months old, and conventional gluten cereal between 7 and 12 months old. | Dietary Supplement: Conventional cereal<br>* Gluten free conventional cereal (from 4 to 6 months old) and conventional cereal with gluten (from 7 to 12 months old)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digestive tolerance | Infant Gastrointestinal Symptom Questionnaire (IGSQ) developed by Riley et al. to be completed by parents/guardians. It contains 13 ítems.For each item there are 5 possible answers in gradation 1 to 5 points and the result is the sum of all of them with minimum scores of 13 (maximum health status) and maximum of 65 | From 4 to 12 months old | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing infant feeding habits | Analysis of daily intake through a record of food consumption for 24 hours | At 4, 5, 6, 9 and 12 months old | 
| Infant microbiota study | Composition, diversity of microbiota. This procedure will be performed by studying samples of feces. | Stool sample collected at 4, 6 and 12 months old. | 
| Assessment of intestinal health | Fecal microbiota profile (fecal pH, butyrate, propionate and acetate) determination | Stool sample collected at 4, 6 and 12 months old. | 
| Assessment of immune-inflammatory response | Record of the IgA secreted in saliva | At 4, 6 and 12 months old. | 
| Infant infection episodes | Specific parent-reported infant symptoms of mild respiratory, gastrointestinal, skin and oropharyngeal infections. Parents will have a dairy to report all symptoms. | At 4, 5, 6, 9 and 12 months old. | 
| Assessment of infant growth: weight | Weight measurements in grams to report anthropometric measures | At 4, 5, 6, 9 and 12 months old. | 
| Assessment of infant growth: lenght | Lenght measurements in centimeters to report anthropometric measures | At 4, 5, 6, 9 and 12 months old. | 
| Assessment of infant growth: cephalic perimeter | Cephalic perimeter measurements in centimeters to report anthropometric measures | At 4, 5, 6, 9 and 12 months old. | 
| Evolution of body composition | Anthropometric measures (brachial perimeter (mm), trichital skin folds and sub-scapular (mm) with compass lipometer) | At 4, 5, 6, 9 and 12 months old | 
| Medical history | Register of: gestational age, anthropometric measures at birth, lactation data and clinical history of interest | At 4 months old | 
| Demographics | Parents' age, parent education level, habits and parents lifestyle, home and social environment | At 4 months old | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gluten, Probiotic, Prebiotic