Combination Probiotic: BB-12 With LGG (Different Doses) in Treating Children With Autism Spectrum Disorder

Study Overview
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Brief Summary
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This protocol is a blinded randomized controlled study of the effects of BB-12 with LGG at different doses in 70 healthy children with autism spectrum disorders at lower and higher doses over an 56-day period and a 28- day observation period. The study is being conducted in order to assess safety and tolerability of the probiotic (BB-12 with LGG) at 2 different doses of BB-12 with LGG. Identifying effects on behaviors in healthy children with ASD using SRS-2 and ABC, GI symptoms using GI symptom severity index, and relevant biomarkers of inflammation, microbiota, and metabolites. Primary testing and procedures will be conducted at the University of Texas Health Science Center at Houston and Memorial Hermann. Biomarker identification includes Integrative analysis of plasma metabolome and stool microbiota will be conducted with the collaboration of Dr. Ruth Ann Luna and Dr. Jim Versalovic at Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology & Microbiology of Baylor College of Medicine.

Official Title
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Road to Discovery for Combination Probiotic BB-12 With LGG (Different Doses) in Treating Autism Spectrum Disorder Disorders

Conditions
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Autism Spectrum Disorder, Gastrointestinal Symptoms

Intervention / Treatment
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* Drug: BB-12 with LGG (Higher Dose)
* Drug: Placebo
* Drug: BB-12 with LGG (Lower Dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children with autism spectrum disorders (4 - 16 years old) and gastrointestinal symptoms, based on the GI Severity Index, with no other recognized illness will be enrolled in this study. There will be no selection on the basis of age, race, or gender. Although the investigators anticipate the majority of subjects will be male and/or pre-pubertal, in females of childbearing potential, a pregnancy test (urine) will be performed on females participating (at each visit). Exclusion Criteria: Pregnancy or breastfeeding Subjects taking immunosuppressive medications, including oral corticosteroids A History of Positive result of HIV, Hepatitis B, and/or Hepatitis C test Abnormal lab test results (Section 5.2) Gastrointestinal diseases such as celiac disease, inflammatory bowel disease Subjects with an allergy to antibiotics Presence of fever or a pre-existing adverse event monitored in the study Use of probiotics in the last 30 days Acute diarrheal illness within the past 30 days Recent (within 2 weeks) or current use of oral antibiotics /anti-fungals Current use of oral laxatives Subjects with implanted prosthetic devices including prosthetic heart valves The investigators will require that subject not take any other probiotic-containing products, including yogurt supplemented with probiotics during the study period.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After psychological screening, the subjects will be randomize children to one of 3 groups. The total number of subject to be enrolled will be 70 healthy children with confirmed ASD status, randomizing each child to placebo (maltodextrin), low daily dose (1 billion cfu's), and higher daily dose (10 billion cfu's) of BB-12+LGG once daily at 1:2:2 ratio. Data will be combined with 30 patients obtained from two funding sources: Texas (THECB) and U.T. pilot project. The data will be combined and an identical design of the placebo and 1 billion cfu dose arms.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BB-12 with LGG (Lower Dose)<br>BB-12 with LGG (Multistrain probiotic; lower dose): 1 billion CFUs | Drug: BB-12 with LGG (Lower Dose)<br>* BB-12 with LGG - Lower Dose (1 billion CFUs)<br>* Other names: Probiotic;|
| Placebo Comparator: Placebo<br>Maltodextrin | Drug: Placebo<br>* Maltodextrin<br>* Other names: Maltodextrin;|
| Active Comparator: BB-12 with LGG (Higher Dose)<br>BB-12 with LGG (Multistrain probiotic: higher dose): 10 billion CFUs | Drug: BB-12 with LGG (Higher Dose)<br>* BB-12 with LGG - Higher Dose (10 billion CFUs)<br>* Other names: Probiotic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of BB-12+LGG at different doses on adverse events (safety) | Adverse events (Safety) will be measured by case report form (survey) that are related to BB-12 with LGG (health-promoting bacteria) or placebo treatment. The symptom grade will detail the severity of adverse events. | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors with Aberrant Behavior Checklist (ABC) | Psychological/Behavioral change in irritability and related maladaptive behaviors associated with ASD will be measured by the Aberrant Behavior Checklist (ABC) pre and post treatment | Days 1, 21, 56 and 84 | 
| Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors measured with the Social Responsiveness Scale-2 | Psychological/Behavioral change in irritability and related maladaptive behaviors associated with ASD will be measured by the and the Social Responsiveness Scale-2 (SRS-2) pre and post treatment. | Days 1, 21, 56 and 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea