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| Name | Class |
|---|---|
| Autism Treatment Network | NETWORK |
| Autism Speaks | OTHER |
A randomized pilot trial of a probiotic for quality of life in autism spectrum disorder (ASD), targeting gastrointestinal (GI) symptoms.
The physical and mental/emotional health of people with autism spectrum disorder (ASD) are closely connected. The emerging data on immune abnormalities and gut microbiome differences, and interactions of the genome with these suggest a possible etiological link between physical and mental dysfunction, especially the gastrointestinal (GI) dysfunction and severe anxiety that many individuals with ASD manifest. The investigators have preliminary clinical evidence that children with ASD & GI symptoms differ in microbiome composition and function from neurotypical children with GI symptoms. The investigators hypothesize that altered host-microbial signals, which include altered fecal neurotransmitter gamma-aminobutyric acid (GABA) levels contribute towards anxiety and sensory over-responsivity in ASD. Our preliminary findings also show that probiotic Visbiome Extra Strength, improves GI and pain symptoms, correlating with altered gut microbiome composition and related metabolites (the macrobiome). The proposed crossover trial will explore the possibilities of this new appreciation of the microbiome-mental/physical function connection for ASD, GI dysfunction, and anxiety. If altering the gut microbiome results in better GI and emotional function, it could improve the quality of life for children with ASD and their parents. A pilot trial with 12 children with ASD will test feasibility for a proposed three-site crossover randomized clinical trial (RCT) of probiotics (beneficial bacteria including Lactobacilli & Bifidobacteria) in 60 children 3-12 years old with ASD, GI dysfunction, & anxiety. In a balanced crossover children will be randomized 1;1 to Visbiome or placebo first, 8 weeks per condition with 3 weeks washout between. The investigators have access to significant fecal microbiome and metabolome data from NIH-funded Human Microbiome Projects (HMP) on similar-age healthy and irritable-bowel children, with and without ASD. These will help leverage our understanding of macrobiome changes that correlate with functional improvement of GI and abdominal pain symptoms. Pilot study efficiency will also benefit from those HMPs having already collected and analyzed baseline stools for some children with ASD, thus saving significant costs for baseline stool analyses for the pilot.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Visbiome, Then Placebo | Experimental | The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data. |
|
| Placebo, Then Visbiome | Placebo Comparator | Placebo matched to probiotic. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Maltose (placebo) | Drug | Maltose with a trace amount of silicon dioxide |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8 | A 74-item survey with 14 scales. Report forms for specific age ranges assess the parent's perception of the child's GI function and/or symptoms during the last month on a 5-point scale from 0 (never a problem) to 4 (almost always a problem). Items are reverse-scored and transformed to a 0-100 scale so lower scores reflect worse GI dysfunction. Response choices are in Likert-scale format ranging from 0 to 4 (0=Never, 1=Almost Never, 2=Sometimes, 3=Often, 4=Almost Always). | Baseline and Week 8 of Both the First and Second Intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Target Symptom Rating From Baseline at Week 8 | Parents are asked to name the 2 problems of most concern to them at baseline; a clinician helps the parent quantify and describe the problem (frequency, duration, severity, interference with daily life) at baseline. At subsequent visits the clinician reminds the parent of the previous description and helps them again quantify/describe the current state. A panel of blind clinicians reviews the descriptions and rates each on a 9-point scale relative to baseline, from remission (0) to disastrously worse (9), with 5=no change. These ratings are averaged, capturing the issues of most concern to parents across families. For purposes of this study, one of the 2 problems will be required to pertain to GI function, and will be analyzed separately as well as being averaged into the overall symptom rating. |
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Inclusion Criteria:
Participants will be recruited from minority, poor, inner city, or rural populations.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eugene Arnold, MD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio State University Wexner Medical Center | Columbus | Ohio | 43210 | United States |
13 patients were randomized to order, but 3 dropped out because of distance and transportation without providing any follow-up data, leaving 10 who progressed through to study completion. (77% retention rate)
13 participants were screened and randomized to be in the study at the OSU Wexner Medical Center, Nisonger Center in 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Visbiome, Then Placebo | Children aged 3-12 years with ASD, GI symptoms, and anxiety were randomly assigned 1:1 to probiotic Visbiome for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment (19 weeks total). The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data. Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety |
| FG001 | Placebo, Then Visbiome | Children aged 3-12 years with ASD, GI symptoms, and anxiety were randomly assigned 1:1 to placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment (19 weeks total). Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (8 Weeks) |
|
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| Washout (3 Weeks) |
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| Second Intervention (8 Weeks) |
|
[Not Specified]
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| ID | Title | Description |
|---|---|---|
| BG000 | Visbiome, Then Placebo | Participants were randomly assigned 1:1 to Visbiome probiotic for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose: the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted. The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data. Visbiome Extra Strength: It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8 | A 74-item survey with 14 scales. Report forms for specific age ranges assess the parent's perception of the child's GI function and/or symptoms during the last month on a 5-point scale from 0 (never a problem) to 4 (almost always a problem). Items are reverse-scored and transformed to a 0-100 scale so lower scores reflect worse GI dysfunction. Response choices are in Likert-scale format ranging from 0 to 4 (0=Never, 1=Almost Never, 2=Sometimes, 3=Often, 4=Almost Always). | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
After Baseline: 4 weeks, 8 weeks, 15 weeks, 19 weeks
Collected AE data from all participants of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Visbiome | Randomly assigned 1:1 probiotic for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted. The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data. Visbiome Extra Strength: A mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal Disorders | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment | Abdominal distension (S:1, P:1)** Abdominal pain (S:1 P:2) Diarrhoea (S:0 P:2) Flatulence (S:3 P:2) Nausea (S:1 P:2) Vomiting (S:1 P:0) ** S= Supplement/Probiotic P = Placebo number is events reported |
Small sample. Crossover did not accurately anticipate the duration of carryover Crossover not the best design for this treatment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. L. Eugene Arnold, MD, MED. Professor Emeritus College of Medicine | Nisonger Center | 614-685-6701 | l.arnold@osumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 19, 2016 | Nov 4, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008320 | Maltose |
| D012822 | Silicon Dioxide |
| ID | Term |
|---|---|
| D005936 | Glucans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D004187 | Disaccharides |
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| Visbiome Extra Strength | Drug | It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety |
|
| Baseline and Week 8 of Both the First and Second Intervention |
| Change in Parent Anxiety Checklist--ASD From Baseline at Week 8 | A 25-item single-factor scale measure of emotional stability/anxiety. Higher scores are worse for PRAS-ASD subscale, hence a negative estimate means more improvement with the probiotics compared to control. Scores range from 0-75. | Baseline and Week 8 of Both the First and Second Intervention |
| Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8 | The ABC is a 58-item parent rating on a 0-3 scale with five subscales:
Higher scores are worse for the ABC subscale, hence a negative estimate means more improvement with the probiotics compared to control. | Baseline and Week 8 of Both the First and Second Intervention |
| Change in Social Responsiveness Scale (SRS) From Baseline at Week 8 | This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. The SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age and will detect changes in core ASD symptoms. A higher score in this scale represents worse symptoms with raw scores summed and generated t-scores ranging from 0-110. | Baseline and Week 8 of Both the First and Second Intervention |
| Children's Sleep Habits Questionnaire (CSHQ) at Week 8 | It includes 33 items rated retrospectively over the previous week by parents yielding a total score and eight subscales. Eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness.Total score (summed) range of 0-99. A higher score is a better outcome for this measure. | Week 8 of Both the First and Second Intervention |
| Change in The Parenting Stress Index Short Form (PSI) | The PSI is used to evaluate the degree of stress in the parent-child relationship. The Short Form has 36 items from the full length PSI, rated on a 5-point scale from 1 = strongly disagree, to 5 = strongly agree. It is completed in 10-15 minutes. The PSI may be used for parents of children up to 12 years. It yields a Total Score and three domain scores. This will detect effect on parental stress and QOL. Higher scores (ranging from 0-180) are worse for PSI, hence a negative estimate means more improvement with the probiotics compared to control. | Baseline and Week 8 of Both the First and Second Intervention |
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| NOT COMPLETED |
|
| BG001 | Placebo, the Visbiome | Particiapants were randomly assigned 1:1 to placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose: the first 4 weeks of the probiotic treatment was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted. Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Gastrointestinal Module of the Pediatric Quality of Life Inventory (PedsQL) | A 74-item survey with 14 scales. Report forms for specific age ranges assess the parent's perception of the child's GI function and/or symptoms during the last month on a 5-point scale from 0 (never a problem) to 4 (almost always a problem). Items are reverse-scored and transformed to a 0-100 scale so lower scores reflect worse GI dysfunction. Response choices are in Likert-scale format ranging from 0 to 4 (0=Never, 1=Almost Never, 2=Sometimes, 3=Often, 4=Almost Always). | Mean | Standard Deviation | units on a scale |
|
| Parent-Rated Anxiety Scale for ASD (PRAS-ASD) | A 25-item single-factor scale measure of emotional stability/anxiety summed to get a score. Higher scores are worse for PRAS-ASD subscale. Scores range from 0-75. | Mean | Standard Deviation | units on a scale |
|
| Aberrant Behavior Checklist (ABC) | The ABC is a 58-item parent rating on a 0-3 scale with five subscales:
Higher scores are worse for the ABC subscale. | Mean | Standard Deviation | units on a scale |
|
| Social Responsiveness Scale (SRS) | This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. The SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age and will detect changes in core ASD symptoms. A higher score in this scale represents worse symptoms with raw scores summed and generated t-scores ranging from 0-110. | Mean | Standard Deviation | units on a scale |
|
| Abbreviated Children's Sleep Habits Questionnaire (CSHQ) | It includes 33 items rated retrospectively over the previous week by parents yielding a total score and eight subscales. Eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness.Total score (summed) range of 0-99. A higher score is a better outcome for this measure. | Mean | Standard Deviation | units on a scale |
|
| Parenting Stress Index Short Form (PSI) | The PSI is used to evaluate the degree of stress in the parent-child relationship. The Short Form has 36 items from the full length PSI, rated on a 5-point scale from 1 = strongly disagree, to 5 = strongly agree. It is completed in 10-15 minutes. The PSI may be used for parents of children up to 12 years. It yields a Total Score and three domain scores. This will detect effect on parental stress and QOL. Higher scores are worse for the PSI with sums ranging from 0-180. | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | Randomly assigned 1:1 placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted. Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide |
|
|
| Secondary | Change in Target Symptom Rating From Baseline at Week 8 | Parents are asked to name the 2 problems of most concern to them at baseline; a clinician helps the parent quantify and describe the problem (frequency, duration, severity, interference with daily life) at baseline. At subsequent visits the clinician reminds the parent of the previous description and helps them again quantify/describe the current state. A panel of blind clinicians reviews the descriptions and rates each on a 9-point scale relative to baseline, from remission (0) to disastrously worse (9), with 5=no change. These ratings are averaged, capturing the issues of most concern to parents across families. For purposes of this study, one of the 2 problems will be required to pertain to GI function, and will be analyzed separately as well as being averaged into the overall symptom rating. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
|
|
| Secondary | Change in Parent Anxiety Checklist--ASD From Baseline at Week 8 | A 25-item single-factor scale measure of emotional stability/anxiety. Higher scores are worse for PRAS-ASD subscale, hence a negative estimate means more improvement with the probiotics compared to control. Scores range from 0-75. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
|
|
| Secondary | Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8 | The ABC is a 58-item parent rating on a 0-3 scale with five subscales:
Higher scores are worse for the ABC subscale, hence a negative estimate means more improvement with the probiotics compared to control. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
|
|
| Secondary | Change in Social Responsiveness Scale (SRS) From Baseline at Week 8 | This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. The SRS provides a clear picture of a child's social impairments, assessing social awareness, social information processing, capacity for reciprocal social communication, social anxiety/avoidance, and autistic preoccupations and traits. It is appropriate for use with children from 4 to 18 years of age and will detect changes in core ASD symptoms. A higher score in this scale represents worse symptoms with raw scores summed and generated t-scores ranging from 0-110. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
|
|
| Secondary | Children's Sleep Habits Questionnaire (CSHQ) at Week 8 | It includes 33 items rated retrospectively over the previous week by parents yielding a total score and eight subscales. Eight subscales include: (1) bedtime resistance (2) sleep onset latency, (3) sleep duration, (4) anxiety around sleep, (5) night awakenings, (6) sleep disordered breathing, (7) parasomnias and (8) morning waking/daytime sleepiness.Total score (summed) range of 0-99. A higher score is a better outcome for this measure. | Posted | Mean | Standard Deviation | Units on a scale | Week 8 of Both the First and Second Intervention |
|
|
|
| Secondary | Change in The Parenting Stress Index Short Form (PSI) | The PSI is used to evaluate the degree of stress in the parent-child relationship. The Short Form has 36 items from the full length PSI, rated on a 5-point scale from 1 = strongly disagree, to 5 = strongly agree. It is completed in 10-15 minutes. The PSI may be used for parents of children up to 12 years. It yields a Total Score and three domain scores. This will detect effect on parental stress and QOL. Higher scores (ranging from 0-180) are worse for PSI, hence a negative estimate means more improvement with the probiotics compared to control. | Posted | Mean | Standard Deviation | Units on a scale | Baseline and Week 8 of Both the First and Second Intervention |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 6 |
| 10 |
| EG001 | Placebo | Randomly assigned 1:1 placebo for 8 weeks, followed by a 3-week washout and an 8 week crossover treatment. (19 weeks total) Starting dose, the first 4 weeks, was a half packet twice daily mixed with food. At 4 week and 15-week visit, there was an option to increase to a full packet twice daily if no effect was noted. Placebo matched to probiotic. Maltose (placebo): Maltose with a trace amount of silicon dioxide | 0 | 10 | 0 | 10 | 4 | 10 |
|
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| D009844 |
| Oligosaccharides |
| D000073893 | Sugars |
| D008903 | Minerals |
| D007287 | Inorganic Chemicals |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |
| D017655 | Silicon Compounds |
| ABC (3) Stereotypy |
|
| ABC (4) Hyperactivity |
|
| ABC (5) Inappropriate Speech |
|