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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder; Gastrointestinal Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: BB-12 with LGG (Lower Dose); Drug: BB-12 with LGG (Higher Dose)

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: J. Marc Rhoads, MD; Phone Number: 713-500-7642; Email: j.marc.rhoads@uth.tmc.edu
• Study Contact Backup: Name: Nicole Fatheree, BBA; Phone Number: 713-500-5669; Email: nicole.fatheree@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UTHealth
      • Contact: Nicole Fatheree, BBA; Phone Number: 713-500-5669; Email: nicole.fatheree@uth.tmc.edu
      • Contact: Jon M Rhoads, M.D.; Phone Number: 713-500-5669; Email: j.marc.rhoads@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of BB-12+LGG at different doses on GI symptoms as measured by GI Symptom Severity Index	GI symptoms will be measured by the GI Severity Index.	Days 1, 21, 56 and 84
Effects of BB-12+LGG at different doses on gut inflammation (S1009A)	Plasma S100A9 will indicate GI and systemic levels of inflammation. S100A9 is a damage-associated molecular pattern molecule (DAMP) released by granulocytes, which is reportedly elevated 2-fold in plasma of children with ASD.	Days 1, 56 and 84
Effects of BB-12+LGG at different doses on gut inflammation (Fecal Calprotectin)	Biological change in fecal calprotectin levels. FC is a highly accurate fecal marker of inflammation.	Days 1, 56 and 84
Effects of BB-12+LGG at different doses on gut inflammation (Plasma Zonulin)	Plasma zonulin, a marker for intestinal permeability ("leaky gut"), which is often associated with inflammation.	Days 1, 56 and 84
Effects of BB-12+LGG at different doses on gut inflammation (IL-8)	IL-8 can be an indicator of gut inflammation; it released from the intestinal epithelial cells during inflammation.	Days 1, 56 and 84
Effects of BB-12+LGG at different doses on fecal microbial community	Using 16S rDNA analysis, this will determine microbial alpha and beta diversity and distribution of the major taxa before and after probiotic treatment.	Days 1, 56 and 84
Effects of BB-12+LGG at different doses on metabolites	This will determine levels of metabolic markers which are reported to be abnormal in autism: fecal amino acids, ammonia, short chain fatty acids (SCFA), and phenols.	Days 1, 56 and 84

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Texas Higher Education Coordinating Board
• Investigators: Principal Investigator: J Marc RHoads, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 2, 2018

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: HSC-MS-17-0995; R01HD095158-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No