The Gut-Brain Study

NCT03426826 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CHLA-18-00065
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if transplant of fecal matter (stool), also known as fecal microbiota transplantation (FMT), from a healthy person into the intestines of children and young adults with Autism Spectrum Disorder (ASD). For this study children between the ages of 5-17years will be recruited over 2 years. Children will be recruited who receive an ASD diagnosis using the gold-standard Autism Diagnosis Observation Schedule -2 (ADOS-2) using module 1, 2 or 3 (none, limited or no moderate expressive language). Children diagnosed with these modules of the ADOS-2 may be at greater risk for GI disorders and rigid-compulsive behaviors. Additional assessment of rigid-compulsive behaviors and social communication will be done using the Repetitive Behavioral Scales-Revised (RBS-R) and Social Responsiveness Scale-2 (SRS-2), respectively. KBIT (the Kaufman Brief Intelligence Test) is used at baseline to obtain patient IQ. Total evaluation time is approximately 90 minutes. Following baseline symptom evaluation, a medical exam will be performed to determine whether each child is expressing specific GI symptoms. In addition, parents will fill out the Questionnaire for Pediatric Gastrointestinal Symptoms- Rome III (QPGS-III). Once an ASD diagnosis is confirmed, FMT treatment will be initiated, which typically occurs within 4-6 weeks of the initial diagnosis. Half 50% of the children (n=5) will receive the equivalent of 50 g of stools from a healthy donor into the jejunum through upper endoscopy and the other 50% off children (n=5) will receive Saline solution as Placebo control through upper endoscopy. Subjects will have a total of 5 visits within 24 weeks including phone call follow up on Day 7 after FMT.

Conditions

Autism Spectrum Disorder (ASD); Gastro-Intestinal Disorder

Keywords

FMT; Gut Microbiome; Fecal Microbiata Transplantation; Autism Spectrum Disorder; 16s rRNA; Gastro-Intestinal Disorder

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measures, safety and tolerability

  The primary Outcome is safety of FMT and also it is measured by any symptom changes in obsessive/compulsive and repetitive behaviors using the RBS-R questionnaire.

  24 weeks

Secondary Outcomes (1)

• Secondary Outcome Measures, symptom improvement

  24 weeks

Study Arms (2)

Arm 1

PLACEBO COMPARATOR

Placebo Comparator placebo into the jejunum through upper endoscopy.

Biological: FMT versus placebo

Arm 2

ACTIVE COMPARATOR

Active Comparator: Donor Stool Transplant Arm 2 will get FMT (Fecal Microbial Transplant) with Healthy Donor Stool into the jejunum through upper endoscopy.

Biological: FMT versus placebo

Interventions

FMT versus placebo BIOLOGICAL

Biological/Vaccine: Fecal Microbial Transplant versus placebo Fecal Transplant via endoscopy. Other Names: FMT

Also known as: fecal microbial transplant vs placebo

Arm 1; Arm 2

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: 5-17 who have been diagnosed with non-syndromic ASD-s
• Needs upper GI endoscopy
• Clinical Assessment of ASD
• ADOS validated diagnoses of ASD
• Questionnaires: RBS-2 , KBIT, SRS, Rome III Version (QPGS- RIII), Ped QL, SSP

You may not qualify if:

• Subjects able to give consent/assent but unwilling to give informed consent/assent
• Prematurity (\<36 weeks)
• Pregnancy: testing will be done on FMT day 0 for subjects with childbearing potential
• Subjects with significant renal and liver dysfunction (creatinine \> 2 mg/dl and direct bilirubin \> 2 mg/dl)
• Subjects with congenital or acquired immunodeficiency, or who are immunosuppressed such as neoplastic disease or organ transplantation), have received or are receiving chemotherapy, or have been diagnosed with HIV.
• Subjects with syndromic disorders of defined genetic cause, and subjects who have severe sensory or motor problems (for example, blindness, deafness, seizures, cerebral palsy)
• Subjects with severe food allergies

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (1)

Children's Hospital Los Angles

Los Angeles, California, 90027, United States

Location

Related Publications (8)

• 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.

  PMID: 28122648 BACKGROUND

• Luna RA, Oezguen N, Balderas M, Venkatachalam A, Runge JK, Versalovic J, Veenstra-VanderWeele J, Anderson GM, Savidge T, Williams KC. Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder. Cell Mol Gastroenterol Hepatol. 2016 Dec 11;3(2):218-230. doi: 10.1016/j.jcmgh.2016.11.008. eCollection 2017 Mar.

  PMID: 28275689 BACKGROUND

• Gorrindo P, Williams KC, Lee EB, Walker LS, McGrew SG, Levitt P. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8. doi: 10.1002/aur.237.

  PMID: 22511450 BACKGROUND

• Gorrindo P, Lane CJ, Lee EB, McLaughlin B, Levitt P. Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction. PLoS One. 2013 Jul 3;8(7):e68444. doi: 10.1371/journal.pone.0068444. Print 2013.

  PMID: 23844202 BACKGROUND

• Yao MD, von Rosenvinge EC, Groden C, Mannon PJ. Multiple endoscopic biopsies in research subjects: safety results from a National Institutes of Health series. Gastrointest Endosc. 2009 Apr;69(4):906-10. doi: 10.1016/j.gie.2008.05.015. Epub 2009 Jan 10.

  PMID: 19136110 BACKGROUND

• Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012 May;107(5):761-7. doi: 10.1038/ajg.2011.482. Epub 2012 Jan 31.

  PMID: 22290405 BACKGROUND

• Finegold SM. Therapy and epidemiology of autism--clostridial spores as key elements. Med Hypotheses. 2008;70(3):508-11. doi: 10.1016/j.mehy.2007.07.019. Epub 2007 Sep 29.

  PMID: 17904761 BACKGROUND

• Finegold SM. State of the art; microbiology in health and disease. Intestinal bacterial flora in autism. Anaerobe. 2011 Dec;17(6):367-8. doi: 10.1016/j.anaerobe.2011.03.007. Epub 2011 Apr 16.

  PMID: 21524713 BACKGROUND

MeSH Terms

Conditions

Autism Spectrum Disorder; Digestive System Diseases

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Sonia Michail, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

• Pat Levitt, Ph.D

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician /Professor of Clinical Pediatrics

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 8, 2018
• Study Start: August 15, 2019
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 2, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)