Combination Probiotic for Autism

Overseen By Nicole Fatheree, BBA

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Immunosuppressants, Corticosteroids, Antibiotics, Antifungals

Disqualifiers: Pregnancy, HIV, Hepatitis, GI diseases, others

Compensation: Varies

Number of Visits: 85

Duration: 8 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination probiotic treatment, BB-12 with LGG, to determine its safety and tolerability in children with autism spectrum disorders (ASD) who also have gastrointestinal issues. Researchers aim to understand how different doses of the probiotic affect behaviors, gut symptoms, and biological markers related to inflammation and gut health. The trial compares two doses of the probiotic to a placebo, a look-alike substance with no active ingredient. Children with ASD who have ongoing gut problems and have not used probiotics in the last month may be suitable for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that participants do not take any other probiotic-containing products, including yogurt with probiotics, during the study. If you are taking immunosuppressive medications, oral corticosteroids, or have used probiotics, oral antibiotics, or antifungals recently, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of probiotics BB-12 and LGG is generally safe. Studies have found no major side effects when used together. BB-12 and LGG rank among the most researched probiotics worldwide. In the USA, they are considered safe to eat, meaning most people can take them without issues.

Even at varying amounts, no strong evidence suggests they cause harm. These probiotics often support gut health and have been tested in many situations. Overall, the safety data appears promising for those considering joining a trial with these probiotics. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for autism focus on behavioral therapy or medications that target symptoms like irritability and hyperactivity. But this new combination probiotic treatment is different because it uses specific strains of beneficial bacteria, BB-12 and LGG, to potentially improve gut health and, in turn, influence brain function. Researchers are excited because this approach taps into the gut-brain connection, which is a relatively new area of exploration in autism. The treatment comes in two doses—one with 1 billion CFUs and a higher dose with 10 billion CFUs—offering a non-invasive option that could complement existing therapies without the side effects often associated with medication.

What evidence suggests that this trial's treatments could be effective for autism?

This trial will compare different doses of the probiotics BB-12 and LGG to a placebo in children with autism. Research has shown that these probiotics might help with autism-related symptoms. Studies have found improvements in gut health, often linked to behavior in children with autism. Additionally, they may protect certain brain cells, suggesting potential benefits for brain-related conditions. Although research remains in the early stages, these findings indicate that the probiotics might benefit children with autism. More research is needed to confirm these effects, but initial results are promising. ^{1 2 6 7 8}

Who Is on the Research Team?

J Marc RHoads, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for healthy children aged 4-16 with autism spectrum disorders and gastrointestinal symptoms, without other illnesses. It's open to all races and genders; girls who can have babies will get a pregnancy test each visit. Kids can't join if they're on laxatives, have certain GI diseases, allergies to antibiotics, fever or serious health issues, are pregnant/breastfeeding, take immune-weakening drugs or had recent antibiotics/probiotics.

Inclusion Criteria

I understand a pregnancy test is required for women who can have children.

My child has autism and GI issues but is otherwise healthy.

Exclusion Criteria

Subjects with an allergy to antibiotics

Subjects with implanted prosthetic devices including prosthetic heart valves

I am currently taking oral laxatives.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BB-12 with LGG at different doses over a 56-day period

8 weeks

Visits on Days 1, 21, and 56

Observation

Participants are observed for effects on behaviors, GI symptoms, and biomarkers

4 weeks

Visit on Day 84

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BB-12 with LGG (Higher Dose)
• BB-12 with LGG (Lower Dose)
• Placebo

Trial Overview The study tests two doses of a combination probiotic (BB-12 with LGG) against a placebo in kids with autism over an 84-day period. Researchers want to see how safe it is and its effect on behavior using the SRS-2 and ABC scales, GI symptoms via the GI symptom severity index, and changes in inflammation markers, gut bacteria & metabolites.

How Is the Trial Designed?

Group I: BB-12 with LGG (Lower Dose) Active Control 1 Intervention

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

Group II: BB-12 with LGG (Higher Dose) Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

Maltodextrin

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Texas Higher Education Coordinating Board

Collaborator

Texas Higher Education Coordinating Board

Collaborator

Trials

4

Recruited

390+

Published Research Related to This Trial

A structured group Life Goals Program (LGP) for 45 bipolar patients showed high satisfaction rates, with 82.4% of participants very satisfied with the information provided during the program.

After one year in the program, participants reported improved mood stability and better strategies for preventing and coping with relapses, as indicated by a significant decrease in their depression scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the life goals group therapy program for bipolar patients: an open study. de Andrés, RD., Aillon, N., Bardiot, MC., et al.[2014]

In a study of 40 children with autism spectrum disorder (ASD) aged 2-5 years, a 3-month probiotic supplementation significantly increased beneficial gut bacteria (Bifidobacterium spp. and Lactobacillus spp.), indicating a positive effect on gut health.

The probiotic treatment was associated with reduced anxiety and improved sleep in 80% of the children, suggesting that probiotics may help alleviate some symptoms of ASD and improve overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Characterization of Probiotics and Their Influence on Children with Autism Spectrum Disorder. Meguid, NA., Mawgoud, YIA., Bjørklund, G., et al.[2022]

Bifidobacterium animalis subsp. lactis BB-12(®) is a well-documented probiotic with over 130 human clinical studies supporting its efficacy in promoting gastrointestinal health and immune function.

BB-12(®) has shown to improve bowel function, protect against diarrhea, and enhance resistance to respiratory infections, demonstrating its beneficial effects on both gut and immune health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Science behind the Probiotic Strain Bifidobacterium animalis subsp. lactis BB-12(®). Jungersen, M., Wind, A., Johansen, E., et al.[2020]

A study involving nine healthy adults and eight milk-hypersensitive adults showed that the gut microbiota of milk-hypersensitive individuals is similar to that of healthy individuals, indicating no significant dysbiosis.

Supplementation with Lactobacillus rhamnosus GG (LGG) for 4 weeks significantly increased bifidobacteria in healthy adults, but not in milk-hypersensitive individuals, suggesting that while LGG can enhance gut flora, its effects may vary based on individual health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the gut bacterial flora of healthy and milk-hypersensitive adults, as measured by fluorescence in situ hybridization. Apostolou, E., Pelto, L., Kirjavainen, PV., et al.[2018]

A structured psychoeducative group program (Life Goals Program) for bipolar patients significantly reduced the number of hospitalizations over a 3-year period, with notable improvements observed after both phase 1 (6 weeks) and phases 1 and 2 (median duration 24 months).

Participants who completed both phases of the program reported greater improvements in mood stability, relapse prevention, and social relationships compared to those who only completed phase 1, indicating the program's effectiveness in enhancing overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term impact of the life goals group therapy program for bipolar patients. Aubry, JM., Charmillot, A., Aillon, N., et al.[2018]

In a four-week study involving boys aged 7-15 with autism spectrum disorder, Lactobacillus plantarum PS128 significantly improved opposition and defiance behaviors compared to a placebo.

Younger children (aged 7-12) showed notable improvements in overall behavior scores after taking PS128, indicating its potential as a beneficial intervention for managing certain symptoms of ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Liu, YW., Liong, MT., Chung, YE., et al.[2023]

The Life Goals Programme (LGP) significantly improved knowledge about bipolar disorder and reduced anxiety levels in participants, with these benefits lasting for at least 6 months after the intervention.

Participants in the LGP showed moderate-to-large improvements in medication adherence and small but significant enhancements in moment-by-moment mood stability compared to those receiving standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Phase 1 of Life Goals Programme on symptom reduction and mood stability for bipolar disorder. So, SH., Mak, AD., Chan, PS., et al.[2021]

A brief group cognitive behavior therapy (CBT-G) intervention showed a trend towards lower recurrence rates of depression in older adults (27.8% vs. 44.4% in controls) after one year, although the results were not statistically significant.

The CBT-G intervention was successfully implemented with satisfactory delivery competence, suggesting it is a promising approach that warrants further evaluation in a larger trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot randomised controlled trial of a brief cognitive behavioural group intervention to reduce recurrence rates in late life depression. Wilkinson, P., Alder, N., Juszczak, E., et al.[2018]

In a study involving 1,909 participants across six clinical trials, the ingestion of specific probiotics, including Lactobacillus rhamnosus GG and its combinations, did not lead to significant adverse events compared to a placebo.

The analysis showed no statistically significant differences in adverse events related to gastrointestinal, respiratory, or infection-related disorders, indicating that these probiotics are likely safe for both young and elderly individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of adverse events in healthy individuals using probiotics--analysis of six randomised studies by one study group. Tapiovaara, L., Lehtoranta, L., Poussa, T., et al.[2022]

A study involving 221 healthy infants aged 3 to 12 months found that three probiotic strains (Bifidobacterium longum subsp. infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052) were safe and well tolerated over an 8-week period, with no serious adverse events reported.

Growth measurements (weight, height, and head circumference) were similar across all groups, indicating that these probiotics do not negatively impact infant growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerance of three probiotic strains in healthy infants: a multi-centre randomized, double-blind, placebo-controlled trial. Manzano, S., De Andrés, J., Castro, I., et al.[2018]

Collaborative care models, which involve teamwork between primary care and psychiatric providers, can enhance both mental health and overall medical outcomes for patients with bipolar disorder.

Key areas for focus in collaborative care for bipolar disorder include suicide risk assessment, substance use monitoring, tracking side effects like extrapyramidal symptoms, metabolic health monitoring, and providing education specific to bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collaborative mental health and primary care for bipolar disorder. Williams, JW., Manning, JS.[2022]

In a study involving 131 autistic children and adolescents, the use of the probiotic Lactobacillus plantarum PS128 led to significant improvements in symptoms of Autism Spectrum Disorder with very few side effects.

Younger children showed more pronounced benefits from Lactobacillus plantarum PS128 compared to other probiotics, supporting its specific efficacy in managing symptoms of autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum PS128 and Other Probiotics in Children and Adolescents with Autism Spectrum Disorder: A Real-World Experience. Mensi, MM., Rogantini, C., Marchesi, M., et al.[2021]

In a study of 41 children with autism spectrum disorder (ASD), combining probiotics with applied behavior analysis (ABA) significantly improved behavioral symptoms compared to ABA alone, as measured by the Autism Treatment Evaluation Checklist (ATEC) after 3 months.

The addition of probiotics also led to beneficial changes in intestinal flora, increasing beneficial bacteria like Bifidobacterium and Lactobacillus while reducing harmful bacteria such as Shigella and Clostridium, suggesting a potential mechanism for the observed improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of probiotics combined with applied behavior analysis in the treatment of children with autism spectrum disorder: a prospective randomized controlled trial. Li, YQ., Sun, YH., Liang, YP., et al.[2023]

A meta-analysis of clinical controlled trials found that probiotics and prebiotics did not significantly improve the severity of autism spectrum disorder (ASD) symptoms, gastrointestinal issues, or comorbid psychopathology in children.

The study highlights the need for more randomized controlled trials with larger populations and professional oversight to verify these findings, as current evidence remains limited and contradictory to previous literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotics and probiotics for autism spectrum disorder: a systematic review and meta-analysis of controlled clinical trials. Song, W., Zhang, M., Teng, L., et al.[2022]

The study found that Bifidobacterium animalis subsp lactis (BB-12) supplemented yogurt is safe and well tolerated by healthy adults taking antibiotics, with no significant differences in adverse events compared to control yogurt.

BB-12 supplementation led to modestly higher levels of the probiotic in feces and some changes in immune cell gene expression, suggesting potential immunomodulatory effects that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study. Merenstein, DJ., Tan, TP., Molokin, A., et al.[2018]

Citations

1. reporter.nih.gov reporter.nih.gov/search/CbJDv1iUREe9GtIwEF5lDw/project-details/9766942

Road to discovery for combination probiotic BB-12 with LGG in ... If an optimal dose of BB-12 + LGG is found to be safe and shows a signal toward improvement with respect to GI or autistic symptoms, we plan to study this ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03514784

Combination Probiotic: BB-12 With LGG (Different Doses) ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29025837/

Effects of Lactobacillus rhamnosus GG and Bifidobacterium ... The aim of the study is to examine the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306452222005498

Chronic Treatment with the Probiotics Lacticaseibacillus ... These results indicate that the mixture of probiotics LGG and BB-12 protects nigrostriatal DA neurons against 6-OHDA-induced damage.

5. researchgate.net researchgate.net/publication/320348683_Effects_of_Lactobacillus_rhamnosus_GG_and_Bifidobacterium_lactis_Bb12_on_beta-cell_function_in_children_with_newly_diagnosed_type_1_diabetes_Protocol_of_a_randomised_controlled_trial

Effects of Lactobacillus rhamnosus GG and Bifidobacterium ... The aim of the study is to examine the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5652563/

Effects of Lactobacillus rhamnosus GG and Bifidobacterium ... L rhamnosus GG and Bifidobacterium lactis Bb12. These are among the world's best-studied probiotics. In the USA, both have received a generally ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/16/NCT03181516/Prot_SAP_000.pdf

Efficacy and Safety of BB-12 Supplemented Strawberry ... Optimized care included pre- and probiotic treatments for 7–14 days before surgery. The prebiotic used was oligofructose and the probiotic.

8. withpower.com withpower.com/trial/phase-2-disease-4-2016-19c09

Combination Probiotic for Autism Research shows that the combination of probiotics BB-12 and LGG is generally safe for human use, with studies indicating no significant adverse effects in both ...