Autism Spectrum Disorder, Gastrointestinal Symptoms
Conditions
Keywords
Autism Spectrum Disorder, ASD, Gastrointestinal Symptoms, Constipation, Diarrhea
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.
Interventions
DRUGBB-12 with LGG (Higher Dose)
BB-12 with LGG - Higher Dose (10 billion CFUs)
DRUGPlacebo
Maltodextrin
DRUGBB-12 with LGG (Lower Dose)
BB-12 with LGG - Lower Dose (1 billion CFUs)
Sponsors
The University of Texas Health Science Center, Houston
Texas Higher Education Coordinating Board
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
4 Years to 16 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as Indicated by Number of Participants With Invasive Infection Resulting From the Administration of Probiotic | from baseline to 56 days | Infection will be determined by clinical observations and temperature measurements made during the study period, as well as complete metabolic panel, complete blood count, and C-reactive protein (CRP) blood testing. |
| Number of Participants With Clinical Tolerance of the Probiotic | from baseline to 56 days | Tolerance will be determined by assessment of symptoms, which will be monitored at clinical research center visits, as well as ability to remain on the treatment. |
| Safety as Indicated by Number of Participants With Toxicity Resulting From the Administration of Probiotic | from baseline to 56 days | Toxicity will be determined by assessment of electrolyte status, renal function \[blood urea nitrogen (BUN) and creatinine (Cr), hepatic toxicity \[transaminases (AST, ALT) and total bilirubin\], and hematologic status \[CBC to measure hemoglobin and absolute neutrophil count\]. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJ Marc RHoads, MD
The University of Texas Health Science Center, Houston
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 92.2 months STANDARD_DEVIATION 31.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 26 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Region of Enrollment United States | 34 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 33 | 0 / 34 |
| other Total, other adverse events | 18 / 33 | 17 / 33 | 10 / 34 |
| serious Total, serious adverse events | 0 / 33 | 0 / 33 | 0 / 34 |
Outcome results
None listed