Autism
Conditions
Keywords
probiotic, prebiotic, autism, oligosaccharides, Bifidobacterium infantis
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTSynbiotic
DIETARY_SUPPLEMENTPrebiotic
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stool Microbiota Composition Change During Prebiotic Only Treatment | Five weeks | 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. |
| Stool Microbiota Composition Change During Synbiotic Treatment | Five weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Immune Profile Change During Prebiotic Only Treatment | Five weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prebiotic Only First, Then Synbiotic 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. | 5 |
| Synbiotic First, Then Prebiotic Only 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. | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Prebiotic Only First, Then Synbiotic | Total | Synbiotic First, Then Prebiotic Only |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 11 Participants | 6 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized African-American, Hispanic/Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized African-American, non-Hispanic | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White, Hispanic/Latino | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White, non-Hispanic | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment United States | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: Five weeks
Population: In the Prebiotic First group, 1 subject withdrew consent prior to providing stool sample. In the Synbiotic First group, 1 subject withdrew consent prior to starting prebiotic treatment, and 1 subject was unable to provide a stool sample for analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Prebiotic Only Treatment | No change in enterotype | 2 Participants |
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Prebiotic Only Treatment | Bifidobacterium to Prevotella | 1 Participants |
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Prebiotic Only Treatment | Bacteroides to Bifidobacterium | 1 Participants |
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Prebiotic Only Treatment | Prevotella to Bifidobacterium | 0 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Prebiotic Only Treatment | Prevotella to Bifidobacterium | 1 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Prebiotic Only Treatment | No change in enterotype | 3 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Prebiotic Only Treatment | Bacteroides to Bifidobacterium | 0 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Prebiotic Only Treatment | Bifidobacterium to Prevotella | 0 Participants |
Primary
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.
Time frame: Five weeks
Population: In the Prebiotic First group, 1 subject withdrew consent prior to starting synbiotic treatment. In the Synbiotic First group, 1 subject withdrew consent prior to providing stool sample, and 1 subject was unable to provide a stool sample for analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Synbiotic Treatment | No change in enterotype | 4 Participants |
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Synbiotic Treatment | Prevotella to Mixed | 0 Participants |
| Prebiotic Only First, Then Synbiotic | Stool Microbiota Composition Change During Synbiotic Treatment | Prevotella to Bifidobacterium | 0 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Synbiotic Treatment | No change in enterotype | 2 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Synbiotic Treatment | Prevotella to Mixed | 1 Participants |
| Synbiotic First, Then Prebiotic Only | Stool Microbiota Composition Change During Synbiotic Treatment | Prevotella to Bifidobacterium | 1 Participants |
Secondary
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.
Time frame: Five weeks
Population: 1 subject was unable to provide blood specimens throughout the study due to significant anxiety with regard to venipuncture, so only 7 subjects' serum was available for analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Prebiotic Only First, Then Synbiotic | Serum Immune Profile Change During Prebiotic Only Treatment | Post-Synbiotic % IL-13 | -0.8 percentage of cytokine production |
| Prebiotic Only First, Then Synbiotic | Serum Immune Profile Change During Prebiotic Only Treatment | Post-Prebiotic % TNF-alpha | -7.9 percentage of cytokine production |