Sponsor: Ohio State University
Autism Treatment Network
Information provided by:
L. Eugene Arnold, Ohio State University
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.
Condition Intervention Phase
Autism Spectrum Disorders Drug: Maltose (placebo) Phase 0
Anxiety Drug: Visbiome Extra Strength
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Resource links provided by NLM:
MedlinePlus related topics: Anxiety Autism Spectrum Disorder
Drug Information available for: Silicon dioxide
U.S. FDA Resources
Further study details as provided by Ohio State University:
Primary Outcome Measures:
Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) (Varni et al., 2001; (Varni, Burwinkle, & Seid, 2006; Varni et al, 2014) [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ] [ Designated as safety issue: No ]
A 74-item survey with 14 scales (# of items): stomach pain & hurt (6 items), discomfort when eating (5), food & drink limits (6), trouble swallowing (3), heartburn/reflux (4), nausea/vomiting (4), gas & bloating (7), constipation (14), blood in poop (2), diarrhea (7), worry about going poop (5), worry about stomachaches (2), medicines (4), and communication (5).
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).
Secondary Outcome Measures:
Change in Target Symptom Rating (Arnold et al, 2003) [ Time Frame: Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ] [ Designated as safety issue: No ]
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 to disastrously worse, 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.
Change in Parent Anxiety Checklist
–-ASD (Scahill, Lecavalier, Bears, & Aman, 2015) [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ] [ Designated as safety issue: No ]
Change in The Aberrant Behavior Checklist (ABC) (Aman et al., 1985a, 1985b) [ Time Frame: Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ] [ Designated as safety issue: No ]
The ABC is a 58-item parent rating on a 0-3 scale with five subscales: 1) Irritability (includes agitation, aggression, and self-injury, 15 items); 2) Social Withdrawal (16 items); 3) Stereotypies (7 items); 4) Hyperactivity (16 items); and 5) Inappropriate Speech (4 items).
Change in Social Responsiveness Scale (SRS) (Costantino et al., 2003) [ Time Frame: Baseline, Week 8, Week 11, Week 19 ] [ Designated as safety issue: No ]
This 65-item rating scale measures the severity of autism spectrum symptoms as they occur in natural social settings. Completed by a parent or teacher in 15 to 20 minutes, 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.
Change in Children’s Sleep Habits Questionnaire (CSHQ) (Owens, Spirito, & Mcguinn, 2000) [ Time Frame: Baseline, Week 8, Week 11, Week 19 ] [ Designated as safety issue: No ]
It includes 33 items rated retrospectively over the previous week by parents. 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. In a recent study of the Autism Treatment Network, 75% of the participants analyzed had a CSHQ score >41, the clinical threshold for sleep problems (Hollway, Aman, and Butter, 2013). Sleep greatly affects quality of life for both children and parents, and it is important to detect any changes in this important vegetative function.
Change in The Parenting Stress Index Short Form (PSI) (Abidin,1995) [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
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.
Other Outcome Measures:
Change in Vital signs [ Time Frame: Screen, Baseline, Week 4, Week 8, Week 11, Week 15, Week 19 ] [ Designated as safety issue: No ]
Estimated Enrollment: 12
Study Start Date: August 2016
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
The probiotic mix (VISBIOME) will be mainly Bifidobacteria and Lactobacilli, in view of the previously reported encouraging clinical studies and safety data.
Drug: Visbiome Extra Strength
It is a mix of 8 strains of beneficial bacteria that should improve gut flora, improving GI function and hopefully anxiety
Placebo Comparator: Placebo
Placebo matched to probiotic.
Drug: Maltose (placebo)
Maltose with a trace amount of silicon dioxide
Other Name: Maltose with silicon dioxide
Ages Eligible for Study: 3 Years to 12 Years (Child)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
- 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.
- 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.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
No Contacts or Locations Provided
Responsible Party: L. Eugene Arnold, Professor Emeritus of Psychiatry, Ohio State University
ClinicalTrials.gov Identifier: NCT02903030 History of Changes
Other Study ID Numbers: 2016H0174
Study First Received: June 14, 2016
Last Updated: September 12, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Ohio State University:
Additional relevant MeSH terms:
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Physiological Effects of Drugs
ClinicalTrials.gov processed this record on September 20, 2016
Verified September 2016 by Ohio State University