Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901.

Probiotics, prebiotics, and synbiotics for patients with autism spectrum disorder: a meta-analysis and umbrella review

“…The study’s results are supported by reputable sources, including Schmitt et al ( 40 ) and Kang et al ( 7 ), which enhances the study’s credibility and strengthens its overall validity. The present paper includes a comprehensive meta-analysis of randomized controlled trials (RCTs) examining the effect of probiotics, prebiotics, and synbiotics on symptoms associated with ASD.…”

“…Of 16 included studies, 15 used probiotics and one used prebiotics. Out of 16, seven were from the USA ( 7 , 40 – 42 , 47 , 50 , 52 ), four from China ( 43 – 45 , 49 ), two from the UK ( 51 , 54 ), one from each Italy, Taiwan, and Egypt ( 39 , 46 , 48 ).…”

Salivary Transcriptome and Mitochondrial Analysis of ASD Children Compared to Healthy Controls

“…The present study included a dietary summary indicating that the healthy USA cohort's rich and diverse diet influenced their overall health. However, prebiotics and probiotic interventions have provided therapeutic benefits without dietary interventions, which would place diet into a more proper perspective [89][90][91]. A randomized clinical trial recently published reported a significant improvement from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during probiotic treatment.…”

Superior performance of biofilm versus planktonic Limosilactobacillus reuteri in protection of the intestines and brain in a piglet model of necrotizing enterocolitis

“…We have produced Good Manufacturing Practice (GMP)-grade Lr in its biofilm state (SB-121; Scioto Biosciences, Inc.) designed for human administration. A recent phase 1b clinical trial demonstrated the safety and tolerability of SB-121 in adults with autism spectrum disorder (ASD) 78 . NEC and ASD are both diseases that involve the gut-brain axis 79 , 80 .…”