FMT in Pediatric Crohn's Disease (FMTPCD)

Safety of FMT in Maintenance of Pediatric Crohn's Disease

The goal of this study is to evaluate the safety of Fecal Microbiota Transplantation (FMT) in children with Crohn's disease who are in remission. Safety will be the primary endpoint and Pediatric Crohn's Disease. Pediatric Crohn's Disease Activity Index (PCDAI) with other secondary endpoints including changes in gut microbial diversity will also be studied. All children will receive the equivalent of 50g of stools from a healthy donor into the jejunum through upper endoscopy. Also, 1-2 additional mucosal biopsies will be collected during patient's routine (standard of care) endoscopy. Subjects will have a total of 5 study visits within 24 weeks including phone call follow up on Day 7 after FMT.

Study Overview

• Status: Completed
• Conditions: Crohn Disease; Pediatric Crohns Disease
• Intervention / Treatment: Biological: FMT

Detailed Description

The Investigators hypothesize that children with Crohn's disease who are in remission can receive a single endoscopic dose of FMT with no significant safety concerns.

All children will receive the equivalent of 50 g of stools from a healthy donor into the jejunum through upper endoscopy. Children will be seen at baseline, then 4 and 24 weeks after study drug administration begins. Stools will be collected and stored for gut microbial profiles during the study visit windows. In addition, a follow up telephone call will be performed 7 days after study drug is administered. If children undergo endoscopy as part of the standard of care, study staff will obtain 1-2 additional biopsies for evaluation of mucosal inflammation. This study will also capture any laboratory results if any of the subjects undergo laboratory testing as part of the standard of care. This study will define the effects of transplant on gut microbial profile using advanced molecular taxonomic approaches. Safety will be closely monitored by solicited (during defined telephone calls and study visits) and unsolicited adverse events (at all times). Safety will be the primary endpoint of this study. Secondary endpoints include Pediatric Crohn's Disease Activity Index (PCDAI), changes in gut microbial diversity - determined by gut microbial genomics and proteomics (16S ribosomal RNA, 16s rRNA), and outcome measures for mucosal inflammation and repair as reflected through laboratory testing such as the level for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), inflammatory cytokines of the colonic mucosa as well as the stool calprotectin level.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age: 7-21 who have been diagnosed with Crohn's disease
2. Remission of disease defined as PCDAI <10
3. Needs upper GI endoscopy

Exclusion Criteria:

1. Unwilling to give informed consent/assent
2. Pregnancy and breast feeding in patient subjects of childbearing potential
3. Subjects with significant renal and liver dysfunction (creatinine > 2 mg/dl and direct bilirubin > 2 mg/dl)
4. Subjects with congenital or acquired immunodeficiency, or who are immunosuppressed due to conditions other than Crohn's disease (such as neoplastic disease or organ transplantation), have received or are receiving chemotherapy, or have been diagnosed with HIV.
5. Subjects with severe food allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMT in children with disease remission; All children (with Crohn's disease in remission) will receive the equivalent of 50 g of stools from a healthy donor (FMT) into the jejunum through upper endoscopy.	Biological: FMT; Fecal Microbiota Transplantation, single dose, 50g of stool, delivered via standard of care upper endoscopy into jejunum.; Other Names: Fecal Microbiota Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Safety will be closely monitored (during defined telephone calls and study visits) and adverse events will be documented, including mucosal inflammation episodes and standard of care laboratory test abnormalities.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crohn's disease activity	PCDAI scores will be collected	24 weeks
Changes in gut microbiome	The effects of transplant on the gut microbial profile will be determined using advanced molecular taxonomic approaches (gut microbial profiling).	24 weeks

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles
• Investigators: Principal Investigator: Sonia Michail, MD, Children's Hospital Los Angeles

Publications and helpful links

General Publications

• Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008 Feb;134(2):577-94. doi: 10.1053/j.gastro.2007.11.059.
• Rinawi F, Assa A, Hartman C, Mozer Glassberg Y, Friedler VN, Rosenbach Y, Silbermintz A, Zevit N, Shamir R. Incidence of Bowel Surgery and Associated Risk Factors in Pediatric-Onset Crohn's Disease. Inflamm Bowel Dis. 2016 Dec;22(12):2917-2923. doi: 10.1097/MIB.0000000000000937.
• Shi Y, Dong Y, Huang W, Zhu D, Mao H, Su P. Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis. PLoS One. 2016 Jun 13;11(6):e0157259. doi: 10.1371/journal.pone.0157259. eCollection 2016.
• Bakhtiar SM, LeBlanc JG, Salvucci E, Ali A, Martin R, Langella P, Chatel JM, Miyoshi A, Bermudez-Humaran LG, Azevedo V. Implications of the human microbiome in inflammatory bowel diseases. FEMS Microbiol Lett. 2013 May;342(1):10-7. doi: 10.1111/1574-6968.12111. Epub 2013 Mar 15.
• D'Inca R, Annese V, di Leo V, Latiano A, Quaino V, Abazia C, Vettorato MG, Sturniolo GC. Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease. Aliment Pharmacol Ther. 2006 May 15;23(10):1455-61. doi: 10.1111/j.1365-2036.2006.02916.x.

Helpful Links

• fecal-microbial-transplant-program at CHLA

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (Actual): June 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; FMT; Crohn's Disease; Gut Microbiome; 16s rRNA; PCDAI
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: CHLA-17-00221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No