FMT in Pediatric Crohn's Disease (FMTPCD)

• ClinicalTrials.gov Identifier: NCT03194529
• Recruitment Status: Completed
• First Posted: June 21, 2017
• Last Update Posted: March 13, 2020
• Sponsor: Children's Hospital Los Angeles
• Information provided by (Responsible Party): Children's Hospital Los Angeles

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Crohn Disease; Pediatric Crohns Disease	Biological: FMT	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Primary outcome is safety in children with Crohn's disease in remission.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Safety of FMT in Maintenance of Pediatric Crohn's Disease
• Actual Study Start Date: October 9, 2017
• Actual Primary Completion Date: June 30, 2019
• Actual Study Completion Date: July 31, 2019

Arms and Interventions

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 Name: Fecal Microbiota Transplantation

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 weeks ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Sponsors and Collaborators

Children's Hospital Los Angeles

Investigators

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

More Information

Additional Information:

fecal-microbial-transplant-program at CHLA 

Publications:

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.

Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008 Feb;134(2):577-94. doi: 10.1053/j.gastro.2007.11.059.

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.

• Responsible Party: Children's Hospital Los Angeles
• ClinicalTrials.gov Identifier: NCT03194529
• Other Study ID Numbers: CHLA-17-00221
• First Posted: June 21, 2017
• Last Update Posted: March 13, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Children's Hospital Los Angeles:

Crohn's Disease; PCDAI; 16s rRNA; Fecal Microbiota Transplantation; Gut Microbiome; FMT

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases