Gastrointestinal Problems, Autism Spectrum Disorders
Conditions
Keywords
children
Brief summary
This is an open-label clinical trial to investigate a combination therapy for treating gastrointestinal problems in children with autism spectrum disorders. The combination therapy includes beneficial bacteria.
Detailed description
This is an open-label clinical trial to evaluate the safety, tolerability, and feasibility of a combination therapy to treat gastrointestinal problems in children with autism spectrum disorders. It involves a combination therapy including beneficial bacteria.
Interventions
DRUGoral Vancomycin
an antibiotic
DRUGMoviPrep
a bowel cleanse
DRUGPrilosec
a stomach acid suppressan
BIOLOGICALhuman fecal material; processed, frozen administered orally
human fecal material; processed, frozen, administered orally
BIOLOGICALhuman fecal material; processed, frozen; administered orally and rectally
human fecal material; processed, frozen; administered orally and rectally
Sponsors
Northern Arizona University
University of Arizona
University of Minnesota
Arizona State University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Children ages 7-17 years 2. Diagnosis of autism per Autism Diagnostic Interview-Revised (ADI-R) 3. Moderate or Severe GI problems ( on the GSRS, a single score of 4 (severe) on any item, or a score of 3 (moderate) on two items, or a score of 2 (mild) or more on any 4 items 4. No changes in medications, supplements, diet, therapies, or education in last 3 months, and no intention to change them during clinical trial 5. General good physical health aside from gastrointestinal problems 6. Cognitive Ability to Provide Informed Assent
Exclusion criteria
1. Antibiotics in last 6 months 2. Probiotics in last 3 months 3. Single-gene disorder (Fragile X, etc.) 4. Major brain malformation 5. Tube feeding 6. Severe gastrointestinal problems that require immediate treatment (life-threatening) 7. Ulcerative Colitis, Crohn's Disease, diagnosed Celiac Disease, Eosinophilic Gastroenteritis, or similar conditions 8. Severely underweight/malnourished 9. Recent or scheduled surgeries 10. Current participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Symptom Responsiveness Scale (GSRS) | Baseline and 10 weeks (end of treatment) | The GSRS is a measure of gastrointestinal symptoms. It includes 15 questions, rated on a Likert scale of 1-7, from no symptoms to severe symptoms, respectively (i.e., higher is worse). We report an average score for all 15 questions, so the possible range for the average score is also 1-7. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Safety Markers (Assessment of Blood Chemistry Panel and Complete Blood Count) | Baseline and 10 weeks (end of treatment) | Number of participants who had a clinically significant change in their blood safety markers (comprehensive metabolic panel including kidney/liver function and complete blood count with differential) |
| Childhood Autism Rating Scale (CARS) | Baseline and 10 weeks (end of treatment) | The CARS is an assessment of 15 autism-related symptoms. Each item is scored on a scale of 1 (no symptoms) to 4 (severe symptoms), and the scores for each symptom are summed to obtain a total score. So, the possible scores range from 15 to 60, with a higher score indicating greater severity. |
| Social Responsiveness Scale (SRS) | Baseline and 10 weeks (end of treatment) | The SRS is an assessment of social skills based on 65 items, where each item is scored on a range of 0 (no symptoms) to 3 (severe symptoms). The total score is a sum of the individual scores, so the total possible range is from 0 to 195, with a higher score indicating greater severity of symptoms. |
| Parent Global Impressions-Revised (PGI-R) | Baseline and 10 weeks (end of treatment) | The PGI-R is a rating of change of 18 autism symptoms compared to baseline, with each symptom rated on a Likert scale from -3 (much worse) to zero (no change) to +3 (much better). We report the average change of the 18 symptoms, so the possible range is from -3 to +3. |
| Vineland Adaptive Behavior Scale (VABS) | baseline and 18 weeks (8 weeks after treatment stopped) | The VABS is an assessment of adaptive behaviors, and we analyzed it to determine the developmental age of the participants, with possible scores ranging from 0 years to 21 years. |
| Daily Stool Record (DSR) | Baseline and 10 weeks (end of treatment) | The DSR is a record of the type of stool that a participant had each day, using the Bristol Stool Form which ranges from 1 (very hard) to 7 (liquid). We then analyzed the data as % days of abnormal stools over a 14 day period, where an abnormal stool is defined as an unusually hard stool (types 1-2), unusually soft stool (types 6-7), or no stool that day. So, the possible range of % days of abnormal stools is from 0% to 100%, with a higher score indicating a more severe problem. |
| Short Sensory Profile | baseline and 10 weeks | The Short Sensory Profile is an assessment of sensory problems. However, the data on this scale was not collected due to administrative error. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Group This group will receive all treatments orally. The treatments include a combination of Vancomycin, MoviPrep, Prilosec, and human fecal material; processed, frozen.
oral Vancomycin: an antibiotic
MoviPrep: a bowel cleanse
Prilosec: a stomach acid suppressan
human fecal material; processed, frozen administered orally: human fecal material; processed, frozen, administered orally | 12 |
| Rectal Group This group will receive some treatments rectally and some orally. The treatments include a combination of Vancomycin, MoviPrep, Prilosec, and human fecal material; processed, frozen.
oral Vancomycin: an antibiotic
MoviPrep: a bowel cleanse
Prilosec: a stomach acid suppressan
human fecal material; processed, frozen; administered orally and rectally: human fecal material; processed, frozen; administered orally and rectally | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Oral Group | Rectal Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 6 Participants | 18 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 12 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 11 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 12 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Gastrointestinal Symptom Responsiveness Scale (GSRS)
The GSRS is a measure of gastrointestinal symptoms. It includes 15 questions, rated on a Likert scale of 1-7, from no symptoms to severe symptoms, respectively (i.e., higher is worse). We report an average score for all 15 questions, so the possible range for the average score is also 1-7.
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on all participants, regardless of how the initial dose of bacteria was administered (oral or rectal).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Group | Gastrointestinal Symptom Responsiveness Scale (GSRS) | Baseline | 2.74 units on a scale | Standard Deviation 0.57 |
| Combined Group | Gastrointestinal Symptom Responsiveness Scale (GSRS) | 10 weeks | 1.31 units on a scale | Standard Deviation 0.45 |
Comparison: Wilcoxon signed rank analysis of symptoms at 10 weeks (end of treatment) vs. baselinep-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Blood Safety Markers (Assessment of Blood Chemistry Panel and Complete Blood Count)
Number of participants who had a clinically significant change in their blood safety markers (comprehensive metabolic panel including kidney/liver function and complete blood count with differential)
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on 18 participants, regardless of how the initial dose of bacteria was administered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Group | Blood Safety Markers (Assessment of Blood Chemistry Panel and Complete Blood Count) | 0 participants |
Secondary
Childhood Autism Rating Scale (CARS)
The CARS is an assessment of 15 autism-related symptoms. Each item is scored on a scale of 1 (no symptoms) to 4 (severe symptoms), and the scores for each symptom are summed to obtain a total score. So, the possible scores range from 15 to 60, with a higher score indicating greater severity.
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on all participants, regardless of how the initial dose of bacteria was administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Group | Childhood Autism Rating Scale (CARS) | Baseline | 39.7 units on a scale | Standard Deviation 5.5 |
| Combined Group | Childhood Autism Rating Scale (CARS) | 10 weeks | 34.1 units on a scale | Standard Deviation 4.7 |
Comparison: Wilcoxon signed-rank test comparing the baseline score vs. the score at 10 weeks (end of treatment).p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Daily Stool Record (DSR)
The DSR is a record of the type of stool that a participant had each day, using the Bristol Stool Form which ranges from 1 (very hard) to 7 (liquid). We then analyzed the data as % days of abnormal stools over a 14 day period, where an abnormal stool is defined as an unusually hard stool (types 1-2), unusually soft stool (types 6-7), or no stool that day. So, the possible range of % days of abnormal stools is from 0% to 100%, with a higher score indicating a more severe problem.
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on all participants, regardless of how the initial dose of bacteria was administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Group | Daily Stool Record (DSR) | Baseline | 62 percentage of days with abnormal stool | Standard Deviation 22 |
| Combined Group | Daily Stool Record (DSR) | 10 weeks | 34 percentage of days with abnormal stool | Standard Deviation 24 |
Comparison: Wilcoxon signed rank test was used to compare scores at baseline vs. at 10 weeks (end of treatment)p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Parent Global Impressions-Revised (PGI-R)
The PGI-R is a rating of change of 18 autism symptoms compared to baseline, with each symptom rated on a Likert scale from -3 (much worse) to zero (no change) to +3 (much better). We report the average change of the 18 symptoms, so the possible range is from -3 to +3.
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on all participants regardless of how the initial dose of bacteria was administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Combined Group | Parent Global Impressions-Revised (PGI-R) | 1.4 units on a scale | Standard Deviation 0.9 |
p-value: <0.001t-test, 2 sided
Secondary
Short Sensory Profile
The Short Sensory Profile is an assessment of sensory problems. However, the data on this scale was not collected due to administrative error.
Time frame: baseline and 10 weeks
Population: Due to a logistical error, this data was not collected
Secondary
Social Responsiveness Scale (SRS)
The SRS is an assessment of social skills based on 65 items, where each item is scored on a range of 0 (no symptoms) to 3 (severe symptoms). The total score is a sum of the individual scores, so the total possible range is from 0 to 195, with a higher score indicating greater severity of symptoms.
Time frame: Baseline and 10 weeks (end of treatment)
Population: We report the data on 18 participants, regardless of how the initial dose of bacteria was administered.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Group | Social Responsiveness Scale (SRS) | Baseline | 116.2 units on a scale | Standard Deviation 24.9 |
| Combined Group | Social Responsiveness Scale (SRS) | 10 weeks | 97.8 units on a scale | Standard Deviation 27.9 |
Comparison: Wilcoxon signed-rank test comparing scores at baseline vs. 10 weeks (end of treatment)p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Vineland Adaptive Behavior Scale (VABS)
The VABS is an assessment of adaptive behaviors, and we analyzed it to determine the developmental age of the participants, with possible scores ranging from 0 years to 21 years.
Time frame: baseline and 18 weeks (8 weeks after treatment stopped)
Population: We report the data on all participants, regardless of how they received the initial dose of bacteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combined Group | Vineland Adaptive Behavior Scale (VABS) | 18 weeks | 6.84 years | Standard Deviation 2.81 |
| Combined Group | Vineland Adaptive Behavior Scale (VABS) | Baseline | 5.39 years | Standard Deviation 2.48 |
Comparison: 2-sided t-test comparing the group at baseline vs. 18 weeks (8 weeks after end of treatment)p-value: <0.001t-test, 2 sided