BBT: Beneficial Bacteria Treatment for Autism

Sponsor
Arizona State University (Other)
Overall Status
Completed
CT.gov ID
NCT02504554
Collaborator
Northern Arizona University (Other), University of Arizona (Other), University of Minnesota (Other)
18
2
21

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: oral Vancomycin
  • Drug: MoviPrep
  • Drug: Prilosec
  • Biological: human fecal material; processed, frozen administered orally
  • Biological: human fecal material; processed, frozen; administered orally and rectally
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Treating Gastrointestinal Problems in Children With Autism Using Beneficial Bacteria Treatment (BBT)
Study Start Date :
Jul 1, 2014
Actual Primary Completion Date :
Apr 1, 2016
Actual Study Completion Date :
Apr 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Oral Group

This group will receive all treatments orally. The treatments include a combination of Vancomycin, MoviPrep, Prilosec, and human fecal material; processed, frozen.

Drug: oral Vancomycin
an antibiotic

Drug: MoviPrep
a bowel cleanse

Drug: Prilosec
a stomach acid suppressan

Biological: human fecal material; processed, frozen administered orally
human fecal material; processed, frozen, administered orally

Experimental: 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.

Drug: oral Vancomycin
an antibiotic

Drug: MoviPrep
a bowel cleanse

Drug: Prilosec
a stomach acid suppressan

Biological: human fecal material; processed, frozen; administered orally and rectally
human fecal material; processed, frozen; administered orally and rectally

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
7 Years to 17 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Arizona State University
  • Northern Arizona University
  • University of Arizona
  • University of Minnesota

Investigators

  • Principal Investigator: James B Adams, PhD, Arizona State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Arizona State University
ClinicalTrials.gov Identifier:
NCT02504554
Other Study ID Numbers:
  • STUDY00001053
First Posted:
Jul 22, 2015
Last Update Posted:
Dec 18, 2019
Last Verified:
Nov 1, 2019
Keywords provided by Arizona State University
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Oral Group Rectal Group
Arm/Group Description 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 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
Period Title: Overall Study
STARTED 12 6
COMPLETED 12 6
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title Oral Group Rectal Group Total
Arm/Group Description 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 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 Total of all reporting groups
Overall Participants 12 6 18
Age (Count of Participants)
<=18 years
12
100%
6
100%
18
100%
Between 18 and 65 years
0
0%
0
0%
0
0%
>=65 years
0
0%
0
0%
0
0%
Sex: Female, Male (Count of Participants)
Female
1
8.3%
1
16.7%
2
11.1%
Male
11
91.7%
5
83.3%
16
88.9%
Region of Enrollment (participants) [Number]
United States
12
100%
6
100%
18
100%

Outcome Measures

1. Primary Outcome
Title Gastrointestinal Symptom Responsiveness Scale (GSRS)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on all participants, regardless of how the initial dose of bacteria was administered (oral or rectal).
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Baseline
2.74
(0.57)
10 weeks
1.31
(0.45)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments Wilcoxon signed rank analysis of symptoms at 10 weeks (end of treatment) vs. baseline
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments no adjustment for multiple hypothesis testing since this was an exploratory study. the p-value listed is the actual result from analysis of the study data.
Method Wilcoxon (Mann-Whitney)
Comments
2. Secondary Outcome
Title Parent Global Impressions-Revised (PGI-R)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on all participants regardless of how the initial dose of bacteria was administered.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Mean (Standard Deviation) [units on a scale]
1.4
(0.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments
Type of Statistical Test Other
Comments paired 2-sided t-test comparing baseline and 10 weeks (end of treatment)
Statistical Test of Hypothesis p-Value <0.001
Comments no adjustment for multiple comparisons
Method t-test, 2 sided
Comments paired t-test, 2 sided
3. Secondary Outcome
Title Blood Safety Markers (Assessment of Blood Chemistry Panel and Complete Blood Count)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on 18 participants, regardless of how the initial dose of bacteria was administered.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Number [participants]
0
0%
4. Secondary Outcome
Title Childhood Autism Rating Scale (CARS)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on all participants, regardless of how the initial dose of bacteria was administered.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Baseline
39.7
(5.5)
10 weeks
34.1
(4.7)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments Wilcoxon signed-rank test comparing the baseline score vs. the score at 10 weeks (end of treatment).
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments no adjustment for multiple comparisons The p-value listed is the result for the actual analysis of the data.
Method Wilcoxon (Mann-Whitney)
Comments
5. Secondary Outcome
Title Social Responsiveness Scale (SRS)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on 18 participants, regardless of how the initial dose of bacteria was administered.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Baseline
116.2
(24.9)
10 weeks
97.8
(27.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments Wilcoxon signed-rank test comparing scores at baseline vs. 10 weeks (end of treatment)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments no adjustment for multiple comparisons the p-value listed is the actual result for the study results.
Method Wilcoxon (Mann-Whitney)
Comments
6. Secondary Outcome
Title Short Sensory Profile
Description 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

Outcome Measure Data

Analysis Population Description
Due to a logistical error, this data was not collected
Arm/Group Title Oral Group Rectal Group
Arm/Group Description 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 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
Measure Participants 0 0
7. Secondary Outcome
Title Vineland Adaptive Behavior Scale (VABS)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on all participants, regardless of how they received the initial dose of bacteria.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Baseline
5.39
(2.48)
18 weeks
6.84
(2.81)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments 2-sided t-test comparing the group at baseline vs. 18 weeks (8 weeks after end of treatment)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments no adjustment for multiple comparisons the p-value listed is the actual result for the analysis of the study data
Method t-test, 2 sided
Comments
8. Secondary Outcome
Title Daily Stool Record (DSR)
Description 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)

Outcome Measure Data

Analysis Population Description
We report the data on all participants, regardless of how the initial dose of bacteria was administered.
Arm/Group Title Combined Group
Arm/Group Description Combination of both groups
Measure Participants 18
Baseline
62
(22)
10 weeks
34
(24)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Combined Group
Comments Wilcoxon signed rank test was used to compare scores at baseline vs. at 10 weeks (end of treatment)
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.002
Comments no adjustment for multiple comparisons
Method Wilcoxon (Mann-Whitney)
Comments

Adverse Events

Time Frame During the 10 weeks of treatment, and the 8 weeks of follow-up (18 weeks total).
Adverse Event Reporting Description
Arm/Group Title All Groups
Arm/Group Description We report the data on 18 participants, regardless of how the initial dose of bacteria was administered. The reason is that all but one of the adverse events occurred during the vancomycin phase, which was common to both groups, and occurred before the randomization to receive the microbiota either orally or rectally. The only exception is one participant who had initial nausea/vomiting upon receiving the initial oral dose of microbiota, and they were switched from the oral group to the rectal group, which they tolerated without incident. There were no adverse effects from the microbiota.
All Cause Mortality
All Groups
Affected / at Risk (%) # Events
Total 0/18 (0%)
Serious Adverse Events
All Groups
Affected / at Risk (%) # Events
Total 0/18 (0%)
Other (Not Including Serious) Adverse Events
All Groups
Affected / at Risk (%) # Events
Total 12/18 (66.7%)
Gastrointestinal disorders
nausea/vomiting 1/18 (5.6%) 1
Nervous system disorders
hyperactivity and/or irritability 12/18 (66.7%) 12
Skin and subcutaneous tissue disorders
rash 1/18 (5.6%) 1

Limitations/Caveats

Small study, open-label design, but able to demonstrate safety and possible efficacy. Dosage and duration not optimized, so adjustments in dosage and/or duration may improve results. Therapy involved 4 medications; not clear if all needed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title James Adams
Organization Arizona State University
Phone 480 965 3316
Email jim.adams@asu.edu
Responsible Party:
Arizona State University
ClinicalTrials.gov Identifier:
NCT02504554
Other Study ID Numbers:
  • STUDY00001053
First Posted:
Jul 22, 2015
Last Update Posted:
Dec 18, 2019
Last Verified:
Nov 1, 2019