- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06290258
Fecal Microbiota Transplantation for Patients With Autism Spectrum Disorder.
Fecal Microbiota Transplantation for Gastrointestinal, Autistic, Emotion, and Behavior Symptoms of Patients With Autism Spectrum Disorder and Gastrointestinal Problems: a Preliminary Study.
Study Overview
Status
Intervention / Treatment
Detailed Description
Autism spectrum disorder (ASD) is an early neuropsychiatric developmental disorder. About 7-90% of patients with ASD have gastrointestinal problems which can relate to abnormal intestinal microbiota. The brain-gut axis can play a key role in the development of brain, and the interaction between microbiota and central nerve system can relate to the pathophysiology of ASD. Fecal Microbiota Transplantation (FMT) has just been used in the treatment of ASD in recent years. It has the potential to improve gastrointestinal, autistic, emotion and behavior symptoms of patients with ASD. Studies of its efficacy are still scarce, and no study has been conducted in Taiwan.
The purpose of this study is to treat patients with ASD by the fecal microbiota transplantation and evaluate its efficacy in gastrointestinal, autistic, emotion and behavior symptoms. It aims to prove the correlations between the brain-gut axis, intestinal microbiota, cytokines and ASD. FMT may improve and change the composition and diversity of intestinal microbiota of patients with ASD and modulate their immune reactions and subsequently improve gastrointestinal, autistic, emotion and behavior symptoms, as well as sleep. Early intervention by FMT in children with ASD may improve their cognition and hence result in better prognosis.
Study design: The investigators will recruit 45 patients with ASD and gastrointestinal problems, aged 6-30 years, who are willing to receive FMT and 1-year regular follow-up. The investigators will collect demographic data, blood and stool samples before and after the intervention, and analyze changes of intestinal microbiota and cytokines. The investigators will use subjective questionnaires to evaluate gastrointestinal, autistic, emotion and behavior symptoms, and objective measurements including actigraphy, intelligence and attention tests to evaluate changes in sleep and cognitive functions. The investigators will analyze the correlations between collected variables and compare the ASD group with the healthy control group at baseline to evaluate group differences. The investigators will evaluate the differences of the intervention group before and after FMT, and also compare the intervention group with the waiting list group, to evaluate the efficacy of FMT. Variables will be presented by mean and percentage. The investigators will use independent sample t-test or Chi-squared test for group comparison. The efficacy of FMT will be analyzed by dependent sample t-test or Wilcoxon signed-rank test, and the investigators will use Pearson correlation coefficient to analyze the correlations between variables.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Wei-Chih Chin
- Phone Number: 3836 +886 3 3281200
- Email: auaug0327@cgmh.org.tw
Study Locations
-
-
-
Taoyuan city, Taiwan, 333423
- Wei-Chih Chin
-
Contact:
- Wei-Chih Chin
- Phone Number: 3836 +886 3 3281200
- Email: auaug0327@cgmh.org.tw
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Diagnosed by a child psychiatrist in line with DSM-5 Autism Spectrum Disorder
- Combined with gastrointestinal problems, any Gastrointestinal Symptoms Rating Scale score≧3.
- Age is between 7-30.
- Participants who are willing to participate in the study and sign the informed consent.
Exclusion Criteria:
- Cases where clinical assessment cannot cooperate with fecal microbiota transplantation and examination.
- Cases requiring antibiotics within 3 months before or after acceptance because of their physiological condition.
- Cases requiring long-term use of proton pump inhibitors due to their physiological conditions.
- Severe physical diseases, such as acute gastrointestinal diseases, severe malnutrition or underweight, immunodeficiency diseases, severe allergies or autoimmune diseases, brain injuries or severe organic brain diseases, will affect the evaluation of treatment results.
- Severe mental illness, such as schizophrenia, bipolar disorder, etc.
- Those who used probiotics one month before the case may affect the intestinal flora.
- Pregnancy.
- Cases that cannot understand the content of this research.
- Participants who are unwilling to participate in the study or refuse to sign the informed consent.
- Participants who are not suitable to include in this study, evaluate by PI or Co-PI.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fecal microbiota transplantation
Children with autism spectrum disorder will receive fecal microbiota transplantation after evaluation.
After the first intervention, the second transplantation will be arranged 6 months later.
|
Fecal microbiota transplantation has been applied to patients with autism spectrum disorder in recent years.
Fecal microbiota of healthy donors can be transplanted to patients through colonoscopy.
Before donation, donors were comprehensively screened to rule out gastrointestinal symptoms and infections.
Patients will receive colon preparation before transplantation.
After the intervention, patients will have to stay in bed and be monitored for 24 hours to assure safety.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes of gastrointestinal symptoms of patients with ASD after FMT
Time Frame: baseline and the 1-year follow-up
|
the Gastrointestinal Symptom Rating Scale, score 15-105, higher scores mean more severe symptom
|
baseline and the 1-year follow-up
|
Changes of autistic symptoms of patients with ASD after FMT
Time Frame: baseline and the 1-year follow-up
|
the Social Responsiveness Scale, score 0-195, higher scores mean more severe symptom
|
baseline and the 1-year follow-up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes of the diversity of intestinal microbiota of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
microbial DNA was extracted from feces by Reagent Kit v3, and the diversity indices were calculated by using the vegan package in R version 3.2.3.
higher indices suggest higher microbial diversity
|
baseline and the 1 year follow-up
|
Changes of cytokine levels of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
cytokine levels
|
baseline and the 1 year follow-up
|
Changes of repetitive behavior symptoms of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Repetitive Behavior Scale-Revised data, higher score suggest more repetitive behavior
|
baseline and the 1 year follow-up
|
Changes of autistic behavior symptoms of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Aberrant Behavior Checklist data, higher score suggest more autistic behavior
|
baseline and the 1 year follow-up
|
Changes of emotion and behavior symptoms of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Child Behavior Checklist Adaptive Behavior Assessment System® - Second Edition data, higher score suggest more emotion and behavior symptoms
|
baseline and the 1 year follow-up
|
Changes of inattention and hyperactivity of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Swanson, Nolan and Pelham IV Scale data, higher score suggest worse attention and more hyperactivity
|
baseline and the 1 year follow-up
|
Changes of quality of life of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the 36-Item Short Form Health Survey data, higher score suggest better quality of life
|
baseline and the 1 year follow-up
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes of objective sleep of patients with ASD after FMT by actigraphy recording
Time Frame: baseline and the 1 year follow-up
|
Participants wear actigraphy for 7-10 days to record their activities and light exposure, which can be calculated to represent their sleep patterns.
Sleep parameters including (total sleep time: minutes, sleep efficiency: percentage, total time in bed: minutes, sleep onset latency: minutes, wakefulness after sleep onset: minutes, the sum of wake duration overnight: minutes, total number of awakenings: times, sleep onset time and wake time: hours and minutes) will be obtained and analyzed.
|
baseline and the 1 year follow-up
|
Changes of subjective sleep of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Children's Sleep Habits Questionnaire data, higher score suggest poorer sleep
|
baseline and the 1 year follow-up
|
Changes of intelligence of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Wechsler Intelligence Scale data, higher score suggest better intelligence
|
baseline and the 1 year follow-up
|
Changes of attention and impulse control of patients with ASD after FMT
Time Frame: baseline and the 1 year follow-up
|
the Conners' Continuous Performance Test data, higher score suggest worse attention and impulse control
|
baseline and the 1 year follow-up
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wei-Chih Chin, Chang Gung Medical Foundation
Publications and helpful links
General Publications
- Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013 Dec 19;155(7):1451-63. doi: 10.1016/j.cell.2013.11.024. Epub 2013 Dec 5.
- Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22. doi: 10.1186/1471-230X-11-22.
- Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.
- Borre YE, O'Keeffe GW, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014 Sep;20(9):509-18. doi: 10.1016/j.molmed.2014.05.002. Epub 2014 Jun 20.
- Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011 Jan;25(1):40-5. doi: 10.1016/j.bbi.2010.08.003. Epub 2010 Aug 10.
- McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83. doi: 10.1542/peds.2013-3995.
- Samsam M, Ahangari R, Naser SA. Pathophysiology of autism spectrum disorders: revisiting gastrointestinal involvement and immune imbalance. World J Gastroenterol. 2014 Aug 7;20(29):9942-51. doi: 10.3748/wjg.v20.i29.9942.
- Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016 Aug 16;11(8):e0161174. doi: 10.1371/journal.pone.0161174. eCollection 2016.
- Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder. Int J Mol Sci. 2022 Jan 25;23(3):1363. doi: 10.3390/ijms23031363.
- Baldi S, Mundula T, Nannini G, Amedei A. Microbiota shaping - the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review. World J Gastroenterol. 2021 Oct 21;27(39):6715-6732. doi: 10.3748/wjg.v27.i39.6715.
- Baxter M, Colville A. Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect. 2016 Feb;92(2):117-27. doi: 10.1016/j.jhin.2015.10.024. Epub 2015 Dec 15.
- Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M. Activation of the inflammatory response system in autism. Neuropsychobiology. 2002;45(1):1-6. doi: 10.1159/000048665.
- Kang DW, Adams JB, Coleman DM, Pollard EL, Maldonado J, McDonough-Means S, Caporaso JG, Krajmalnik-Brown R. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019 Apr 9;9(1):5821. doi: 10.1038/s41598-019-42183-0.
- Li N, Chen H, Cheng Y, Xu F, Ruan G, Ying S, Tang W, Chen L, Chen M, Lv L, Ping Y, Chen D, Wei Y. Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study. Front Cell Infect Microbiol. 2021 Oct 19;11:759435. doi: 10.3389/fcimb.2021.759435. eCollection 2021. Erratum In: Front Cell Infect Microbiol. 2021 Nov 23;11:801376.
- Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, Altaye M, Wills-Karp M. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006 Mar;172(1-2):198-205. doi: 10.1016/j.jneuroim.2005.11.007. Epub 2005 Dec 19.
- Souders MC, Mason TB, Valladares O, Bucan M, Levy SE, Mandell DS, Weaver TE, Pinto-Martin J. Sleep behaviors and sleep quality in children with autism spectrum disorders. Sleep. 2009 Dec;32(12):1566-78. doi: 10.1093/sleep/32.12.1566.
- Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, Jousson O, Leoncini S, Renzi D, Calabro A, De Filippo C. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017 Feb 22;5(1):24. doi: 10.1186/s40168-017-0242-1.
- Tan Q, Orsso CE, Deehan EC, Kung JY, Tun HM, Wine E, Madsen KL, Zwaigenbaum L, Haqq AM. Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review. Autism Res. 2021 Sep;14(9):1820-1836. doi: 10.1002/aur.2560. Epub 2021 Jun 26.
- Xu M, Xu X, Li J, Li F. Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Front Psychiatry. 2019 Jul 17;10:473. doi: 10.3389/fpsyt.2019.00473. eCollection 2019.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 202202143A0
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastrointestinal Diseases
-
Umeå UniversityRecruitingFunctional Gastrointestinal DisorderSweden
-
The University of Texas Medical Branch, GalvestonCompletedGastrointestinal Disorders, Functional
-
Campus Bio-Medico UniversityRecruitingGastrointestinal Cancer | Gastrointestinal Hemorrhage | Gastrointestinal Lesions | Gastrointestinal Injury | Gastrointestinal Perforation | Gastrointestinal UlcerItaly
-
Chang Gung Memorial HospitalNew Bellus EnterprisesUnknownNeoplasm | Functional Gastrointestinal DisorderTaiwan
-
Dr Anne PayneUniversity of LondonUnknownFunctional Gastrointestinal Disorders in ChildrenUnited Kingdom
-
Massachusetts General HospitalEnrolling by invitationGastrointestinal Dysfunction | Gastrointestinal DiseaseUnited States
-
Jiangxi University of Traditional Chinese MedicineThe First Affiliated Hospital of Nanchang University; Second Affiliated Hospital... and other collaboratorsCompletedGastrointestinal DiseaseChina
-
Virginia Commonwealth UniversityRecruitingFunctional Gastrointestinal DisordersUnited States
-
Assiut UniversityNot yet recruitingFunctional Gastrointestinal Disorders
-
Massachusetts General HospitalMassachusetts Institute of TechnologyEnrolling by invitationFunctional Gastrointestinal DisordersUnited States
Clinical Trials on Fecal microbiota transplantation
-
Madhusudan (Madhu) Grover, MBBSRecruiting
-
Medical University of GrazBristol-Myers SquibbTerminatedMalignant Melanoma Stage III | Malignant Melanoma Stage IV | Fecal Microbiota TransplantationAustria
-
Children's Mercy Hospital Kansas CityUniversity of Pittsburgh; Stanford UniversityCompletedUlcerative Colitis (UC) | Inflammatory Bowel Diseases (IBD) | Crohn's Disease (CD)United States
-
The Second Hospital of Nanjing Medical UniversitySIR RUN RUN hospital of Nanjing Medical UniversityNot yet recruitingAttention-deficit/Hyperactivity DisorderChina
-
The Second Hospital of Nanjing Medical UniversityNot yet recruiting
-
The Second Hospital of Nanjing Medical UniversitySIR RUN RUN hospital of Nanjing Medical UniversityRecruiting
-
The Second Hospital of Nanjing Medical UniversityRecruitingCancer | Intestinal ComplicationsChina
-
The First Affiliated Hospital of Nanchang UniversityCompletedAcute Pancreatitis | Intestinal Bacteria Flora Disturbance | Fecal Microbiota Transplantation | Intestinal DysfunctionChina
-
The Second Hospital of Nanjing Medical UniversityWithdrawnCOVID-19 Complicated With Refractory Intestinal InfectionsChina
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingAllogeneic Hematopoietic Stem CellUnited States