Clinical trial NCT04942522: Application of Probiotic PS128 in Children With ASD
Official title: Application of Probiotic PS128 (Lactobacillus Plantarum, PS128) in Children With Autism Spectrum Disorder (ASD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Keywords: ASD
probiotics
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to explore the role of probiotics PS128 in improving gastrointestinal dysfunction and core behavioral symptoms in children with ASD, and investigate the underlying etiological mechanisms of ASD.

Detailed description: After being informed about the study and potential risks, all patients giving written informed consent will undergo screening period to determine eligibility for study entry. Participants who meet the eligibility requirements will be randomized in a double-blind manner(participant and investigator) in a 1:1 ratio to probiotics PS128 group or placebo group. Each patient acts as his or her own control, and they receive both the study drug as well as the placebo. After a washout period, the participants will be switched throughout to different treatments（probiotics placebo group or PS128 group）.

Eligibility criteria: Inclusion Criteria:

1. Children aged 2-5 years with ASD from Tongji hospital (both boys and girls);
2. meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and ADOS-2 diagnostic criteria;
3. No significant abnormalities on head MRI or EEG;
4. If psychotropic medication is required during the project, the psychiatrist must confirm that medication is stable during this period (no change in dose or type of medication);
5. Willing to provide samples such as blood, urine and feces.

Exclusion Criteria:

1. Take antibiotics or antifungal drugs within 15 days prior to the project.
2. Take probiotic products within 30 days prior to the project.
3. Have acute diarrhea within 30 days prior to the project.
4. Start taking new psychotropic medication within 15 days prior to the project.
5. Have severe hearing, visual or motor impairment.
6. Accompany with other mental behavioral disorders, such as schizophrenia, bipolar disorder.
7. A history of Rett syndrome, chromosomal, inherited metabolic disorders and other significant somatic disorders.
8. A history of organic gastrointestinal disorders (e.g., gastroesophageal reflux, food allergies, inflammatory bowel disease), history of intestinal surgery, intestinal obstruction, intestinal perforation, intestinal bleeding, multi-organ failure, and severe immunodeficiency disorders
9. Have a special diet (e.g., gluten-free diet, casein-free diet, ketogenic diet, etc.)
10. Co-morbidities in children with ASD were documented and discussed in detail by two or more behavioral developmental behaviorists, and children with ASD who required immediate rehabilitation or neurological analogs for co-morbidities were not allowed to enter this study.

Primary outcomes:
measure: change in Autism Diagnostic Observation Scale (ADOS)
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: change in Social Responsiveness Scale (SRS)
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in Social Communication Questionnaire (SCQ)
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in the Autism Behavior Checklist (ABC)
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in the Childhood Autism Rating Scale (CARS)
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in Gesell developmental scale
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in frequency of child behavioral problems
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Change in frequency of ASD symptoms
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: change in gastrointestinal symptoms among children with ASD
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
Secondary outcomes:
measure: Cytokine Analysis
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
measure: Evaluate changes of type, number and structural composition of gut microorganisms in children with ASD.
timeFrame: Baseline, 8 weeks, 12 weeks and 20 weeks
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Yan Hao, PhD
role: STUDY_CHAIR
References:
citation: Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 2012 Jun;5(3):160-79. doi: 10.1002/aur.239. Epub 2012 Apr 11.
citation: Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009 Jun;65(6):591-8. doi: 10.1203/PDR.0b013e31819e7203.
citation: Xu G, Strathearn L, Liu B, O'Brien M, Kopelman TG, Zhu J, Snetselaar LG, Bao W. Prevalence and Treatment Patterns of Autism Spectrum Disorder in the United States, 2016. JAMA Pediatr. 2019 Feb 1;173(2):153-159. doi: 10.1001/jamapediatrics.2018.4208.
citation: Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995 Jan;25(1):63-77. doi: 10.1017/s0033291700028099.
citation: Ronald A, Hoekstra RA. Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):255-74. doi: 10.1002/ajmg.b.31159. Epub 2011 Jan 13.
citation: de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016 Apr;22(4):345-61. doi: 10.1038/nm.4071.
citation: Grafodatskaya D, Chung B, Szatmari P, Weksberg R. Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry. 2010 Aug;49(8):794-809. doi: 10.1016/j.jaac.2010.05.005. Epub 2010 Jul 3.
citation: Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000 Jun;30(3):205-23.
citation: Frazier TW, Klingemier EW, Beukemann M, Speer L, Markowitz L, Parikh S, Wexberg S, Giuliano K, Schulte E, Delahunty C, Ahuja V, Eng C, Manos MJ, Hardan AY, Youngstrom EA, Strauss MS. Development of an Objective Autism Risk Index Using Remote Eye Tracking. J Am Acad Child Adolesc Psychiatry. 2016 Apr;55(4):301-9. doi: 10.1016/j.jaac.2016.01.011. Epub 2016 Feb 4.
citation: Lai MC, Lombardo MV, Auyeung B, Chakrabarti B, Baron-Cohen S. Sex/gender differences and autism: setting the scene for future research. J Am Acad Child Adolesc Psychiatry. 2015 Jan;54(1):11-24. doi: 10.1016/j.jaac.2014.10.003. Epub 2014 Oct 16.
citation: Shattuck PT, Durkin M, Maenner M, Newschaffer C, Mandell DS, Wiggins L, Lee LC, Rice C, Giarelli E, Kirby R, Baio J, Pinto-Martin J, Cuniff C. Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study. J Am Acad Child Adolesc Psychiatry. 2009 May;48(5):474-483. doi: 10.1097/CHI.0b013e31819b3848.
citation: Reinhardt VP, Wetherby AM, Schatschneider C, Lord C. Examination of sex differences in a large sample of young children with autism spectrum disorder and typical development. J Autism Dev Disord. 2015 Mar;45(3):697-706. doi: 10.1007/s10803-014-2223-6.
citation: Rose AJ, Rudolph KD. A review of sex differences in peer relationship processes: potential trade-offs for the emotional and behavioral development of girls and boys. Psychol Bull. 2006 Jan;132(1):98-131. doi: 10.1037/0033-2909.132.1.98.