Trial Outcomes & Findings for Effect of Milk Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Children With Autism (NCT NCT02086110)
NCT ID: NCT02086110
Last Updated: 2019-08-01
Results Overview
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.
COMPLETED
NA
11 participants
Five weeks
2019-08-01
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
|
Overall Study
COMPLETED
|
4
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Effect of Milk Oligosaccharides and Bifidobacteria on the Intestinal Microflora of Children With Autism
Baseline characteristics by cohort
| Measure |
Prebiotic Only First, Then Synbiotic
n=5 Participants
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.
|
Synbiotic First, Then Prebiotic Only
n=6 Participants
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.
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White, non-Hispanic
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American, non-Hispanic
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White, Hispanic/Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American, Hispanic/Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Five weeksPopulation: 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.
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.
Outcome measures
| Measure |
Prebiotic Only First, Then Synbiotic
n=4 Participants
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.
|
Synbiotic First, Then Prebiotic Only
n=4 Participants
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.
|
|---|---|---|
|
Stool Microbiota Composition Change During Prebiotic Only Treatment
Prevotella to Bifidobacterium
|
0 Participants
|
1 Participants
|
|
Stool Microbiota Composition Change During Prebiotic Only Treatment
No change in enterotype
|
2 Participants
|
3 Participants
|
|
Stool Microbiota Composition Change During Prebiotic Only Treatment
Bifidobacterium to Prevotella
|
1 Participants
|
0 Participants
|
|
Stool Microbiota Composition Change During Prebiotic Only Treatment
Bacteroides to Bifidobacterium
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Five weeksPopulation: 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.
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.
Outcome measures
| Measure |
Prebiotic Only First, Then Synbiotic
n=4 Participants
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.
|
Synbiotic First, Then Prebiotic Only
n=4 Participants
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.
|
|---|---|---|
|
Stool Microbiota Composition Change During Synbiotic Treatment
No change in enterotype
|
4 Participants
|
2 Participants
|
|
Stool Microbiota Composition Change During Synbiotic Treatment
Prevotella to Bifidobacterium
|
0 Participants
|
1 Participants
|
|
Stool Microbiota Composition Change During Synbiotic Treatment
Prevotella to Mixed
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Five weeksPopulation: 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.
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.
Outcome measures
| Measure |
Prebiotic Only First, Then Synbiotic
n=7 Participants
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.
|
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.
|
|---|---|---|
|
Serum Immune Profile Change During Prebiotic Only Treatment
Post-Synbiotic % IL-13
|
-0.8 percentage of cytokine production
Interval -2.073 to -0.524
|
—
|
|
Serum Immune Profile Change During Prebiotic Only Treatment
Post-Prebiotic % TNF-alpha
|
-7.9 percentage of cytokine production
Interval -14.375 to -1.425
|
—
|
Adverse Events
Prebiotic Only Arm
Synbiotic Arm
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Prebiotic Only Arm
n=10 participants at risk
Includes reported adverse events for all subjects while receiving prebiotic only (bovine milk oligosaccharides, administered orally twice per day for a daily total of 0.3 g per pound of body weight).
|
Synbiotic Arm
n=10 participants at risk
Includes reported adverse events for all subjects while receiving 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).
|
|---|---|---|
|
Gastrointestinal disorders
Increased gassiness
|
20.0%
2/10 • Number of events 2 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
20.0%
2/10 • Number of events 2 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Gastrointestinal disorders
Stomachache
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
0.00%
0/10 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Psychiatric disorders
Sleep disturbances
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
0.00%
0/10 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
2/10 • Number of events 4 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
20.0%
2/10 • Number of events 4 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Gastrointestinal disorders
Constipation
|
20.0%
2/10 • Number of events 4 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
20.0%
2/10 • Number of events 4 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Gastrointestinal disorders
Pain associated with bowel movements
|
30.0%
3/10 • Number of events 3 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
30.0%
3/10 • Number of events 3 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Gastrointestinal disorders
Bloating
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
20.0%
2/10 • Number of events 2 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Psychiatric disorders
Lethargy
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
0.00%
0/10 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Metabolism and nutrition disorders
Weight gain
|
0.00%
0/10 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
20.0%
2/10 • Number of events 2 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
|
Skin and subcutaneous tissue disorders
Hives
|
0.00%
0/10 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
10.0%
1/10 • Number of events 1 • Adverse event data was collected from time of consent through end-of-treatment (12 weeks total).
|
Additional Information
Dr. Kathleen Angkustsiri
University of California, Davis Health System
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place