- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02903030
Probiotics for Quality of Life in Autism Spectrum Disorders
January 24, 2020 updated by: L. Eugene Arnold, Ohio State University
A randomized pilot trial of a probiotic for quality of life in autism spectrum disorder (ASD), targeting gastrointestinal (GI) symptoms.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
13
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Wexner Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 years to 12 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- have DSM-5 ASD on clinical evaluation by a doctoral-level diagnostician, confirmed by Autism Diagnostic Interview-Revised or Autism Diagnostic Observation Schedule;
- be between 3 and 12 years old;
- have >2 mo. abdominal pain, constipation, diarrhea, and/or vomiting, with an item-mean score >2 on at least one scale of the GI module of the PedsQL scale;
- have clinical anxiety symptoms with an item mean of >1.0 (0-3 scale) on the new Autism Anxiety Scale.
Participants will be recruited from minority, poor, inner city, or rural populations.
Exclusion Criteria:
- Antibiotics in 2 months prior to enrolling;
- Prior bowel surgery;
- Chronic serious medical condition (e.g., diabetes);
- Weight or height < 3rd %ile for age;
- Chronic anti-inflammatory use within 2 months prior to enrolling;
- History of inflammatory bowel disease, Celiac disease, or eosinophilic disorders (e.g., eosinophilic esophagitis);
- Already taking probiotics within the previous 6 months.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Visbiome, Then Placebo
The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.
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It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety
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Placebo Comparator: Placebo, Then Visbiome
Placebo matched to probiotic.
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Maltose with a trace amount of silicon dioxide
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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).
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Baseline and Week 8 of Both the First and Second Intervention
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Target Symptom Rating From Baseline at Week 8
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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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Baseline and Week 8 of Both the First and Second Intervention
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Change in Parent Anxiety Checklist--ASD From Baseline at Week 8
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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.
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Baseline and Week 8 of Both the First and Second Intervention
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Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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
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Change in Social Responsiveness Scale (SRS) From Baseline at Week 8
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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.
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Baseline and Week 8 of Both the First and Second Intervention
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Children's Sleep Habits Questionnaire (CSHQ) at Week 8
Time Frame: Week 8 of Both the First and Second Intervention
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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.
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Week 8 of Both the First and Second Intervention
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Change in The Parenting Stress Index Short Form (PSI)
Time Frame: Baseline and Week 8 of Both the First and Second Intervention
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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.
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Baseline and Week 8 of Both the First and Second Intervention
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Eugene Arnold, MD, Ohio State University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2016
Primary Completion (Actual)
December 1, 2017
Study Completion (Actual)
December 1, 2017
Study Registration Dates
First Submitted
June 14, 2016
First Submitted That Met QC Criteria
September 12, 2016
First Posted (Estimate)
September 16, 2016
Study Record Updates
Last Update Posted (Actual)
February 5, 2020
Last Update Submitted That Met QC Criteria
January 24, 2020
Last Verified
January 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016H0174
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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