Combination Probiotic: BB-12 With LGG (Different Doses) in Treating Children With Autism Spectrum Disorder
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03514784|
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : November 17, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Autism Spectrum Disorder Gastrointestinal Symptoms||Drug: BB-12 with LGG (Higher Dose) Drug: Placebo Drug: BB-12 with LGG (Lower Dose)||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|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.|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||The head statistician and study pharmacist will be aware of randomization scheme. The investigators will use an adaptive minimization program for randomization that balances the 3 study arms with respect to distributions of sex and age (4-10 vs. 11-16 y.o.). Patients will be randomized to placebo, 1 billion CFU, and 10 billion CFU study arms at a ratio of 1:2:2. (Currently marketed over-the-counter probiotics typically contain 0.1-50 billion CFUs per dose.) The performance of our covariate adaptive randomization algorithm will be verified through simulation studies before implementation.|
|Official Title:||Road to Discovery for Combination Probiotic BB-12 With LGG (Different Doses) in Treating Autism Spectrum Disorder Disorders|
|Actual Study Start Date :||May 2016|
|Estimated Primary Completion Date :||September 2025|
|Estimated Study Completion Date :||September 2025|
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 Name: Probiotic
Placebo Comparator: Placebo
Other Name: Maltodextrin
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 Name: Probiotic
- Effects of BB-12+LGG at different doses on adverse events (safety) [ Time Frame: 84 days ]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.
- Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors with Aberrant Behavior Checklist (ABC) [ Time Frame: Days 1, 21, 56 and 84 ]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
- Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors measured with the Social Responsiveness Scale-2 [ Time Frame: Days 1, 21, 56 and 84 ]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.
- Effects of BB-12+LGG at different doses on GI symptoms as measured by GI Symptom Severity Index [ Time Frame: Days 1, 21, 56 and 84 ]GI symptoms will be measured by the GI Severity Index.
- Effects of BB-12+LGG at different doses on gut inflammation (S1009A) [ Time Frame: Days 1, 56 and 84 ]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.
- Effects of BB-12+LGG at different doses on gut inflammation (Fecal Calprotectin) [ Time Frame: Days 1, 56 and 84 ]Biological change in fecal calprotectin levels. FC is a highly accurate fecal marker of inflammation.
- Effects of BB-12+LGG at different doses on gut inflammation (Plasma Zonulin) [ Time Frame: Days 1, 56 and 84 ]Plasma zonulin, a marker for intestinal permeability ("leaky gut"), which is often associated with inflammation.
- Effects of BB-12+LGG at different doses on gut inflammation (IL-8) [ Time Frame: Days 1, 56 and 84 ]IL-8 can be an indicator of gut inflammation; it released from the intestinal epithelial cells during inflammation.
- Effects of BB-12+LGG at different doses on fecal microbial community [ Time Frame: Days 1, 56 and 84 ]Using 16S rDNA analysis, this will determine microbial alpha and beta diversity and distribution of the major taxa before and after probiotic treatment.
- Effects of BB-12+LGG at different doses on metabolites [ Time Frame: Days 1, 56 and 84 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03514784
|Contact: J. Marc Rhoads, MDemail@example.com|
|Contact: Nicole Fatheree, BBAfirstname.lastname@example.org|
|Principal Investigator:||J Marc RHoads, MD||The University of Texas Health Science Center, Houston|