Effect of Milk Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Children With Autism

Study Overview
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Brief Summary
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The purpose of this study is to determine the tolerability of dietary supplements and if these supplements can promote a healthy bacterial environment in the intestines of children with autism spectrum disorders and gastrointestinal complaints.

Detailed Description
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This study investigates the feasibility, tolerability, and effects of a dietary supplement on the intestinal flora of children with autism spectrum disorders. This study is divided into two parts, each five weeks long, with a two week break in between. During one part of the study, a prebiotic (milk oligosaccharides from bovine colostrum) will be given. During the other part of the study, the synbiotic composed of the prebiotic and probiotic (bifidobacterium infantis) will be given. Stool will be analyzed at the end of each study arm to determine content of bifidobacteria. On May 8, 2018, we updated the study start and completion dates to the actual (instead of anticipated) dates. On May 30-31, 2019, we updated the study results section.

Official Title
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A Pilot Study Examining Microbiota Composition in Children With Autism and Gastrointestinal Symptoms After Use of Bifidobacterium Infantis and Milk Oligosaccharides

Conditions
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Autism

Intervention / Treatment
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* Dietary Supplement: Synbiotic
* Dietary Supplement: Prebiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Autism Diarrhea and/or constipation Exclusion Criteria: Milk protein or other documented food allergy Lactose intolerance Compromised Immunity GI conditions (inflammatory bowel disease, celiac disease, short gut, etc.) Systemic steroid, antifungal, or antibiotic use within a month of starting the study Failure to thrive Medically prescribed diets or supplements (including probiotic use within the past month). Vegetarian or dairy restricted diet Other medical conditions (seizures, genetic disorders, liver/pancreatic disease, cystic fibrosis, etc.) Medications that interfere or alter intestinal motility or microbiota composition. Full scale intelligence quotient (IQ) <40

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prebiotic only first, then synbiotic<br>This group will receive prebiotic only (bovine milk oligosaccharides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the first five weeks, followed by a two week break with no treatment, and then will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the next five weeks. | Dietary Supplement: Synbiotic<br> <br> * Other names: bovine colostrum, bovine oligosaccharides;Dietary Supplement: Prebiotic<br> <br> * Other names: bovine colostrum, bovine oligosaccharides;|
| Active Comparator: Synbiotic first, then prebiotic only<br>This group will receive the synbiotic (Bifidobacterium infantis (10 billion CFU) twice a day plus 0.3 g per pound body weight of bovine milk oligosaccharides in two divided doses per day orally) for the first five weeks, followed by a two week break with no treatment, and then will receive the prebiotic only (bovine milk oligosacharrides, administered orally twice per day for a daily total of 0.3 g per pound of body weight) for the next five weeks. | Dietary Supplement: Synbiotic<br> <br> * Other names: bovine colostrum, bovine oligosaccharides;Dietary Supplement: Prebiotic<br> <br> * Other names: bovine colostrum, bovine oligosaccharides;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool Microbiota Composition Change During Prebiotic Only Treatment | The stool microbiome composition will be analyzed through next generation sequencing and quantitative polymerase chain reaction. Overall bacterial composition change is reported here, as change in enterotype from before prebiotic only treatment to after prebiotic treatment, for all subjects. Enterotypes were organized into four categories for analysis: a community high in Prevotella (Prevotella), a community high in Bifidobacterium (Bifidobacterium), a community high in Bacteroides (Bacteroides), and a mixed community (Mixed) that did not fall into one of the other three enterotypes but instead consisted of a varied combination of bacteria, including among others Akkermansia, Collinsela, Prevotella, and/or Bacteroides. | Five weeks | 
| Stool Microbiota Composition Change During Synbiotic Treatment | The stool microbiome composition will be analyzed through next generation sequencing and quantitative polymerase chain reaction. Overall bacterial composition change is reported here, as change in enterotype from before synbiotic treatment to after synbiotic treatment, for all subjects. Enterotypes were organized into four categories for analysis: a community high in Prevotella (Prevotella), a community high in Bifidobacterium (Bifidobacterium), a community high in Bacteroides (Bacteroides), and a mixed community (Mixed) that did not fall into one of the other three enterotypes but instead consisted of a varied combination of bacteria, including among others Akkermansia, Collinsela, Prevotella, and/or Bacteroides. | Five weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Immune Profile Change During Prebiotic Only Treatment | Luminex technology will be used to determine a serum immune profile of each participants in response to the study supplement. This profile included assessment of change in percentage of stimulated CD4+ T cells producing intracellular IL-13 before and after Synbiotic treatment (Post-Synbiotic % IL-13), and assessment of change in percentage of stimulated CD8+ T cells producing TNF-alpha before and after Prebiotic Only treatment (Post-Prebiotic % TNF-alpha). Results are reported here for all subjects regardless of treatment order assignment. Decrease in inflammatory cytokines IL-13 and TNF-alpha is interpreted as a positive outcome. | Five weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotic, prebiotic, autism, oligosaccharides, Bifidobacterium infantis