Clinical trial NCT02903030: Probiotics for Quality of Life in Autism Spectrum Disorders
Official title: Probiotics for Quality of Life in Autism Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Autism Spectrum Disorders
Anxiety
Keywords: Gastrointestinal Microbiome
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: Autism Treatment Network
name: Autism Speaks
First posted: 2016-09-16
Enrollment: 13
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: A randomized pilot trial of a probiotic for quality of life in autism spectrum disorder (ASD), targeting gastrointestinal (GI) symptoms.

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.

Eligibility criteria: Inclusion Criteria:

1. have DSM-5 ASD on clinical evaluation by a doctoral-level diagnostician, confirmed by Autism Diagnostic Interview-Revised or Autism Diagnostic Observation Schedule;
2. be between 3 and 12 years old;
3. 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;
4. 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:

1. Antibiotics in 2 months prior to enrolling;
2. Prior bowel surgery;
3. Chronic serious medical condition (e.g., diabetes);
4. Weight or height \< 3rd %ile for age;
5. Chronic anti-inflammatory use within 2 months prior to enrolling;
6. History of inflammatory bowel disease, Celiac disease, or eosinophilic disorders (e.g., eosinophilic esophagitis);
7. Already taking probiotics within the previous 6 months.

Primary outcomes:
measure: Change in Gastrointestinal (GI) Module of the Pediatric Quality of Life Inventory (PedsQL) at From Baseline at Week 8
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
Secondary outcomes:
measure: Change in Target Symptom Rating From Baseline at Week 8
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
measure: Change in Parent Anxiety Checklist--ASD From Baseline at Week 8
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
measure: Change in The Aberrant Behavior Checklist (ABC) From Baseline at Week 8
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
measure: Change in Social Responsiveness Scale (SRS) From Baseline at Week 8
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
measure: Children's Sleep Habits Questionnaire (CSHQ) at Week 8
timeFrame: Week 8 of Both the First and Second Intervention
measure: Change in The Parenting Stress Index Short Form (PSI)
timeFrame: Baseline and Week 8 of Both the First and Second Intervention
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Eugene Arnold, MD
role: PRINCIPAL_INVESTIGATOR
References: