Randomized Trial Comparing Single vs. Maintenance Fecal Microbiota Transplant for Refractory Crohn's Disease in Children

NCT03747718 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CMH-17010048
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

NCT02108821 Primary goal:

• To determine the safety of fecal transplant by colonoscopy and retention enemas for induction followed by maintenance retention fecal vs. placebo enemas in children and young adults with uncomplicated mild-moderately active Crohn's disease. Secondary goals:
• Assess efficacy of this induction regimen followed by maintenance fecal or placebo transplants in responders. The efficacy will be assessed by clinical evaluation and fecal calprotectin that is a non-invasive biomarker.
• Correlate subject's baseline microbiome findings with likelihood for response to FMT induction therapy.
• Follow the chronological microbiome shifts after transplant and correlate with response using clinical and calprotectin assessment in the two groups.

Conditions

Crohn Disease

Keywords

Crohn's; Pediatric; IBD; Fecal

Outcome Measures

Primary Outcomes (1)

• Safety as assessed by Adverse events

  The symptom diary will be used for the subject to document any adverse events that occur during the trial. This will be reviewed at each study visit. Number of participants with treatment related adverse events as assessed by CTCAE v 4.0

  6 months

Secondary Outcomes (4)

• Efficacy as assessed by Physician Global Assessment (PGA)

  6 months

• Efficacy as assessed by PCDAI (Pediatric crohn's disease Activity Index)analysis

  6 months

• Response as assessed by fecal calprotectin

  Calprotectin will be measures at baseline, 1.5 month and 6 months (+/- 2 weeks) after transplantation

• Response as assessed by fecal microbiota changes

  Microbiome will be measures at baseline, 1.5, 3.5 and 6 months (+/- 2 weeks) after transplantation

Study Arms (2)

Fecal Microbiota Follow up Enemas

EXPERIMENTAL

In this arm subjects will receive 3 fecal microbiota transplants at 1 monthly intervals at 1.5, 2.5 and 3.5 months (+/- 2 weeks) after transplant

Biological: Fecal Microbiota Transplantation

Placebo Enemas

PLACEBO COMPARATOR

In this arm subjects will receive 3 placebo transplants at 1 monthly intervals at 1.5, 2.5 and 3.5 months (+/- 2 weeks) after transplant

Other: Placebo

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

Fecal Microbiota Transplantation via colonoscopy for the first transplant in all subjects. This will be followed by 2 fecal enema transplants for all subjects 7 days (+/- 3 days) after colonoscopy. All subjects will be assessed 1.5 months (+/- 2 weeks) after colonoscopy. The subjects who are deemed responders based on a drop in PCDAI=12.5 or higher will be randomized to receive fecal or placebo enemas at 1 monthly (+/- 2 weeks) enemas at 1.5, 2.5 and 3.5 months after colonoscopy. All subjects will be assessed at 4.5 and 6 months (+/- 2 weeks) following colonoscopy. The study will be completed at 6 months (+/- 2 weeks) following colonoscopy.

Fecal Microbiota Follow up Enemas

Placebo OTHER

Fecal Microbiota Transplantation via colonoscopy for the first transplant in all subjects. This will be followed by 2 fecal enema transplants for all subjects 7 days (+/- 3 days) after colonoscopy. All subjects will be assessed 1.5 months (+/- 2 weeks) after colonoscopy. The subjects who are deemed responders based on a drop in PCDAI=12.5 or higher will be randomized to receive fecal or placebo enemas at 1 monthly (+/- 2 weeks) enemas at 1.5, 2.5 and 3.5 months after colonoscopy. All subjects will be assessed at 4.5 and 6 months (+/- 2 weeks) following colonoscopy. The study will be completed at 6 months (+/- 2 weeks) following colonoscopy.

Placebo Enemas

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female subjects between the age of 2 and 25 years.
• Current CD patients who have either:
• o CD with mild to moderately active disease (PCDAI 10-37.5) due to failure of current therapy that has been stable for 4 weeks and are undergoing colonoscopy. For this study we will recruit only those CD patients who have disease only in colon or colon and terminal ileum so disease can be accurately assessed prior to and after FMT.
• The ability to safely undergo colonoscopy (physical status classification of one through three used by the American Society of Anesthesiologists, see Appendix A) as determined by Principal Investigator.
• Females of childbearing potential must have a negative urine pregnancy test during screening and a negative urine pregnancy test at visit 2 (FMT procedure day).
• Informed consent and assent (per IRB/EC), as appropriate.
• Subject must be willing to comply with all study related procedures, follow up visits and complete home diaries.

You may not qualify if:

• Severe immunosuppression: concomitant steroids (1mg/kg/day or greater than 30 mg/day) and biologicals like infliximab, Adalimumab, Golimumab, Certolizuman, Ustekinemab.
• Neutropenia (500 neutrophils/mL) or other severe immunosuppression. Anti-TNF will be permitted. Patients on monoclonal antibodies to B and T cells, calcineurin inhibitors (tacrolimus, cyclosporine) and mycophenolate mofetil may be enrolled only after consultation with the medical monitor.
• Established central line or planned placement during trial.
• Pressor or ventilator support.
• On antibiotics with the inability to discontinue within 4 weeks prior to FMT procedure.
• Requires continued antibiotic use or anticipates antibiotic use in upcoming 4 weeks.
• Patients found to have complications such as an abscess, phlegmon, stricture, small bowel obstruction, perforation, internal or external fistulation or infection as causes for flare up.
• Not willing or able to consent or follow guidelines throughout research trial.
• Non-English Speaking
• Worsening Inflammatory Bowel disease between time of consenting and FMT resulting in PCDAI greater than 40, or are unable to wait for the routine procedure due to rapid deterioration.
• A condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the results of the study
• Participation in an investigational drug study within 30 days of screening.
• Change in therapy within the previous 30 days.
• Female patients of childbearing age who are pregnant, lactating, or plan to become pregnant during study.
• Active or gastrointestinal infection at time of enrollment.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Alka Goyal, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Masking will be completed at the 1.5 month visit by the pharmacy.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Pediatrics

Model Details: The study will operate as a single group open label study until visit 6, at which point it will become a randomized trial.

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: November 20, 2018
• Study Start: December 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

US (1)