Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis

NCT03006809 | Completed Phase 1 FDA Drug

• 1 other identifier: 16-20066
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective unblinded, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment.

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis; FMT; fecal transplant

Outcome Measures

Primary Outcomes (2)

• The occurrence of a Serious Adverse event (SAE), solicited and unsolicited AE, new gastrointestinal medical condition and diagnoses from FMT treatment or new infection from FMT treatment

  safety endpoint

  up to 1 year

• Steroid-free Clinical Remission at week 9 + endoscopic remission or response defined as total Mayo score ≤ 2 with all four sub-scores ≤ 1 and a ≥ 1 point reduction in endoscopy sub-score

  8 weeks post initial treatment

Secondary Outcomes (9)

• Changes in microbiome with FMT therapy. Changes in the microbiome: assessed by frequent stool sampling for 16S rRNA analysis prior to each FMT therapy and after the last capsule/enema dose

  up to 1 year

• Clinical Response: decrease in Mayo score by ≥ 3 points, decrease in bleeding subscore by ≥ 1, or absolute subscore of 0-1

  8 weeks post initial treatment

• Progression of disease defined by initiation of anti-TNF agents or Corticosteroids: Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab, vedolizumab and steroids). Includes time gap until additional agents are started.

  2, 4 and 8 weeks post initial FMT

• Progression of disease defined by increase in dosages of current UC medications

  2, 4 and 8 weeks post initial FMT

• Progression of disease defined by time to colectomy

  up to one year post initial FMT

Study Arms (4)

1

EXPERIMENTAL

pretreatment antibiotics + FMT delivered by colonoscopy + FMT capsules per week x 6 weeks

Biological: Fecal Microbiota Transplantation (FMT), OpenBiome; Other: pretreatment antibiotics

2

EXPERIMENTAL

no antibiotics, FMT delivered by colonoscopy + FMT capsules per week x 6 weeks

Biological: Fecal Microbiota Transplantation (FMT), OpenBiome

3

EXPERIMENTAL

pretreatment antibiotics + FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks

Biological: Fecal Microbiota Transplantation (FMT), OpenBiome; Other: pretreatment antibiotics

4

EXPERIMENTAL

no antibiotics, FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks

Biological: Fecal Microbiota Transplantation (FMT), OpenBiome

Interventions

Fecal Microbiota Transplantation (FMT), OpenBiome BIOLOGICAL

Delivered by colonoscopy, enema or orally (as capsules)

1; 2; 3; 4

pretreatment antibiotics OTHER

5 day course (vancomycin PO 500mg bid, metronidazole PO 500mg bid, and neomycin PO 500mg bid) starting 6 days prior FMT

Also known as: vancomycin, metronidazole, neomycin

1; 3

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with history of mild to moderate Ulcerative Colitis confirmed by endoscopy and pathology.
• Total Mayo score 4-9, endoscopic subscore ≥1; patients who have not had endoscopic evaluation within one year of enrollment will have flexible sigmoidoscopy for evaluation.
• Age 18 - 64 and deemed otherwise healthy at the discretion of the investigator.
• Concurrent therapies with mesalamine (stable x 4 weeks), immunomodulators (stable x 3 months), and biologic agents (stable x 3 months) will be allowed to continue during study.
• If patient is on prednisone, the dose must be ≤ 10mg/day at the time of treatment and will be weaned by 2.5mg/week during the study period.

You may not qualify if:

• Severe or refractory UC defined as Mayo score ≥10, endoscopic disease activity score 3
• Untreated enteric infection (positive stool test for any of the following: Clostridium difficile, Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic E. coli or other enteric infection at the discretion of the investigator.
• History of colectomy
• Disease limited to distal proctitis
• Patients taking probiotics within 6 weeks of planned FMT therapy.
• Severe immunodeficiency, inherited or acquired (e.g. HIV, chemotherapy or radiation therapy)
• Patients with the following laboratory abnormalities: absolute neutrophil count (ANC) \< 1000 / µl, platelets \<50 x 10\^9 /L,, hemoglobin \<6.5 g/dL..
• History of anaphylaxis (severe allergic reaction) to food allergens (e.g. tree nuts, shellfish)
• Dysphagia (oropharyngeal, esophageal, functional, neuromuscular)
• History of recurrent aspiration episodes
• Documented severe gastroparesis
• Active intestinal obstruction
• Patients with renal insufficiency (GFR \< 50ml/min)
• Allergy to the following generally regarded as safe ingredients (GRAS): glycerol, acid resistant HPMC, gellan gum, cocoa butter, titanium dioxide
• Adverse event attributable to any previous FMT

Sponsors & Collaborators

• Najwa Elnachef: lead

Study Sites (1)

UCSF Division of Gastroenterology at Mount Zion

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Smith BJ, Piceno Y, Zydek M, Zhang B, Syriani LA, Terdiman JP, Kassam Z, Ma A, Lynch SV, Pollard KS, El-Nachef N. Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis. Sci Rep. 2022 Apr 1;12(1):5517. doi: 10.1038/s41598-022-09307-5.

  PMID: 35365713 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Fecal Microbiota Transplantation; Vancomycin; Metronidazole; Neomycin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: December 30, 2016
• Study Start: March 2, 2017
• Primary Completion: May 4, 2020
• Study Completion: April 4, 2021
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)