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

Primary Purpose

Autism Spectrum Disorder, Gastrointestinal Symptoms

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BB-12 with LGG (Higher Dose)

Placebo

BB-12 with LGG (Lower Dose)

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea

Eligibility Criteria

4 Years - 16 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

UTHealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Arm Label

BB-12 with LGG (Lower Dose)

Placebo

BB-12 with LGG (Higher Dose)

Arm Description

BB-12 with LGG (Multistrain probiotic; lower dose): 1 billion CFUs

Maltodextrin

BB-12 with LGG (Multistrain probiotic: higher dose): 10 billion CFUs

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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.

Full Information

NCT ID

NCT03514784

First Posted

January 26, 2018

Last Updated

June 8, 2022

Sponsor

The University of Texas Health Science Center, Houston

Collaborators

Texas Higher Education Coordinating Board, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

1. Study Identification

Unique Protocol Identification Number

NCT03514784

Brief Title

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

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 2016 (Actual)

Primary Completion Date

September 2025 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

Collaborators

Texas Higher Education Coordinating Board, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorder, Gastrointestinal Symptoms

Keywords

Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigator

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.

Allocation

Randomized

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

BB-12 with LGG (Lower Dose)

Arm Type

Active Comparator

Arm Description

BB-12 with LGG (Multistrain probiotic; lower dose): 1 billion CFUs

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Maltodextrin

Arm Title

BB-12 with LGG (Higher Dose)

Arm Type

Active Comparator

Arm Description

BB-12 with LGG (Multistrain probiotic: higher dose): 10 billion CFUs

Intervention Type

Drug

Intervention Name(s)

BB-12 with LGG (Higher Dose)

Other Intervention Name(s)

Probiotic

Intervention Description

BB-12 with LGG - Higher Dose (10 billion CFUs)

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Maltodextrin

Intervention Description

Maltodextrin

Intervention Type

Drug

Intervention Name(s)

BB-12 with LGG (Lower Dose)

Other Intervention Name(s)

Probiotic

Intervention Description

BB-12 with LGG - Lower Dose (1 billion CFUs)

Primary Outcome Measure Information:

Title

Effects of BB-12+LGG at different doses on adverse events (safety)

Description

Time Frame

84 days

Secondary Outcome Measure Information:

Title

Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors with Aberrant Behavior Checklist (ABC)

Description

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

Time Frame

Days 1, 21, 56 and 84

Title

Effects of BB-12+LGG at different doses on irritability and maladaptive behaviors measured with the Social Responsiveness Scale-2

Description

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.

Time Frame

Days 1, 21, 56 and 84

Other Pre-specified Outcome Measures:

Title

Effects of BB-12+LGG at different doses on GI symptoms as measured by GI Symptom Severity Index

Description

GI symptoms will be measured by the GI Severity Index.

Time Frame

Days 1, 21, 56 and 84

Title

Effects of BB-12+LGG at different doses on gut inflammation (S1009A)

Description

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.

Time Frame

Days 1, 56 and 84

Title

Effects of BB-12+LGG at different doses on gut inflammation (Fecal Calprotectin)

Description

Biological change in fecal calprotectin levels. FC is a highly accurate fecal marker of inflammation.

Time Frame

Days 1, 56 and 84

Title

Effects of BB-12+LGG at different doses on gut inflammation (Plasma Zonulin)

Description

Plasma zonulin, a marker for intestinal permeability ("leaky gut"), which is often associated with inflammation.

Time Frame

Days 1, 56 and 84

Title

Effects of BB-12+LGG at different doses on gut inflammation (IL-8)

Description

IL-8 can be an indicator of gut inflammation; it released from the intestinal epithelial cells during inflammation.

Time Frame

Days 1, 56 and 84

Title

Effects of BB-12+LGG at different doses on fecal microbial community

Description

Using 16S rDNA analysis, this will determine microbial alpha and beta diversity and distribution of the major taxa before and after probiotic treatment.

Time Frame

Days 1, 56 and 84

Title

Effects of BB-12+LGG at different doses on metabolites

Description

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.

Time Frame

Days 1, 56 and 84

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

J. Marc Rhoads, MD

Phone

713-500-7642

j.marc.rhoads@uth.tmc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Nicole Fatheree, BBA

Phone

713-500-5669

nicole.fatheree@uth.tmc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

J Marc RHoads, MD

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

UTHealth

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jon M Rhoads, M.D.

Phone

713-500-5669

j.marc.rhoads@uth.tmc.edu

First Name & Middle Initial & Last Name & Degree

Nicole Fatheree, BBA

Phone

713-500-5669

nicole.fatheree@uth.tmc.edu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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