Clinical trial NCT03514784: Combination Probiotic: BB-12 With LGG (Different Doses) in Treating Children With Autism Spectrum Disorder
Official title: Road to Discovery for Combination Probiotic BB-12 With LGG (Different Doses) in Treating Autism Spectrum Disorder Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Autism Spectrum Disorder
Gastrointestinal Symptoms
Keywords: Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Texas Higher Education Coordinating Board
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-05-02
Enrollment: 70
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Effects of BB-12+LGG at different doses on adverse events (safety)
timeFrame: 84 days
Secondary outcomes:
measure: Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors with Aberrant Behavior Checklist (ABC)
timeFrame: Days 1, 21, 56 and 84
measure: Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors measured with the Social Responsiveness Scale-2
timeFrame: Days 1, 21, 56 and 84
Other outcomes:
measure: Effects of BB-12+LGG at different doses on GI symptoms as measured by GI Symptom Severity Index
timeFrame: Days 1, 21, 56 and 84
measure: Effects of BB-12+LGG at different doses on gut inflammation (S1009A)
timeFrame: Days 1, 56 and 84
measure: Effects of BB-12+LGG at different doses on gut inflammation (Fecal Calprotectin)
timeFrame: Days 1, 56 and 84
measure: Effects of BB-12+LGG at different doses on gut inflammation (Plasma Zonulin)
timeFrame: Days 1, 56 and 84
measure: Effects of BB-12+LGG at different doses on gut inflammation (IL-8)
timeFrame: Days 1, 56 and 84
measure: Effects of BB-12+LGG at different doses on fecal microbial community
timeFrame: Days 1, 56 and 84
measure: Effects of BB-12+LGG at different doses on metabolites
timeFrame: Days 1, 56 and 84
Locations:
city: Houston
country: United States
facility: UTHealth
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: J Marc RHoads, MD
role: PRINCIPAL_INVESTIGATOR
References: