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LFMT vs Placebo in New Biologic Start for Ulcerative Colitis

Primary Purpose

Ulcerative Colitis

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Lyophilized fecal microbiota (LFMT)
Placebo
Sponsored by
University of Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis focused on measuring FMT, Microbiome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 18 years of age or older but less than 75 years of age
  2. Able to provide informed consent
  3. Established ulcerative colitis diagnosis determined by a physician through standard endoscopic and histologic criteria
  4. Active UC defined as total Mayo score between 6-12 AND Mayo endoscopic sub-score >1 with disease that extends 15 cm or more from the anal verge

  5. Selected by treating physician for initiation of biologic treatment with either vedolizumab or ustekinumab. Patients must be:

    • Biologic naive; OR
    • Have failed anti-TNF, anti-integrin, anti IL12/23 or oral small molecules
  6. Use of effective contraception method for women of childbearing potential for at least 4 weeks prior to receiving study treatment and for the duration of the trial
  7. Willing and able to comply with all required study procedures

Exclusion Criteria:

  1. Severe UC requiring hospitalization
  2. Indeterminate colitis
  3. Evidence of or treatment for C difficile infection or other intestinal pathogen, including CMV, within 4 weeks prior to enrollment
  4. Evidence of toxic megacolon or gastrointestinal perforation on imaging

  5. Abdominal surgery within the past 60 days

    • Neutropenia with absolute neutrophil count <0.5 x 109/L
    • Peripheral white blood cell count > 35.0 x 109/L and fever (>38 degrees Celsius)
    • Planned or actively taking another investigational product
    • Uncontrolled medical conditions such as psychiatric disorders or substance abuse
    • Severe underlying disease such that the patient is not expected to survive for at least 30 days
  6. Pregnant or lactating
  7. Unwilling to discontinue non-dietary probiotic
  8. Antibiotic use in the past 30 days or anticipated need for systemic antibiotic use during study
  9. FMT within 3 months prior to enrollment

  10. Use of the following medications:

    1. rectal/topical therapy within 2 weeks of screening
    2. cyclosporine, tacrolimus or thalidomide within 4 weeks of screening
    3. tofacitinib within 4 weeks of screening
    4. adalimumab or infliximab within 8 weeks of screening
    5. vedolizumab within 8 weeks of screening
    6. ustekinumab within 12 weeks of screening
    7. prednisone > 30 mg/d
  11. Investigator deems enrolment in the study is not in the best interest of the patient

Sites / Locations

  • University of Alberta HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

LFMT capsules + vedolizumab

Placebo capsules + vedolizumab

LFMT capsules + ustekinumab

Placebo capsules + ustekinumab

Arm Description

The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.

The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.

The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.

The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.

Outcomes

Primary Outcome Measures

Proportion of participants with serious adverse events (SAEs) of interest up to week 8 in each group (ie vedolizumab with or without LFMT, ustekinumab with or without LFMT).
SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT

Secondary Outcome Measures

Proportion of participants in each group with adverse events during the study up to week 24, including nausea, vomiting, abdominal pain, worsening diarrhea, constipation or fevers
Proportion of participants who achieve clinical remission, defined as total Mayo score ≤ 2 with no individual subscore > 1, at week 8 and 24 in each group.
Proportion of participants who achieve clinical response
Defined as a reduction in the Mayo clinic score of ≥ 3 points and/ or ≥ 30% from baseline, with a decrease in the rectal bleeding subscore of ≥ 1 point or a subscore ≤ 1 at week 8 and 24 in each group
Proportion of participants who achieve symptom remission, defined as partial Mayo score < 2 with no individual subscore > 1, at week 8 and 24 in each group
Proportion of participants who achieve symptom response, defined as reduction in partial Mayo score ≥ 2 points from baseline and ≥ 30% from baseline and decrease in rectal bleeding score of ≥ 1point from baseline, at week 8 and 24 in each group
Proportion of participants who achieve endoscopic improvement, defined as Mayo endoscopic subscore ≤1, at week 8 and 24 in each group
Changes in partial Mayo score over time up to week 24 relative to baseline in each group
Changes in quality of life, assessed by short IBD Questionnaire (sIBDQ), and work productivity, assessed by Work Productivity and Activity Impairment Questionnaire (WPAIQ), at week 8 and 24 relative to baseline in each group
Changes in inflammatory markers (serum c-reactive protein (CRP) and fecal calprotectin) over time up to week 24 in each group

Full Information

First Posted
March 25, 2022
Last Updated
June 2, 2023
Sponsor
University of Alberta
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1. Study Identification

Unique Protocol Identification Number
NCT05327790
Brief Title
LFMT vs Placebo in New Biologic Start for Ulcerative Colitis
Official Title
A Dual-center, Double Blind, Randomized Placebo-controlled Pilot Trial of Concomitant Lyophilized Fecal Microbiota Transplantation (LFMT) and Biologic Therapy (Vedolizumab or Ustekinumab) for the Induction of Remission in Ulcerative Colitis (UC)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2022 (Actual)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To compare the safety and efficacy of concomitant LFMT versus placebo in UC patients who are starting vedolizumab or ustekinumab.
Detailed Description
This is dual-center, randomized, double-blind, placebo-controlled pilot trial for UC patients with active disease who are being initiated on treatment with vedolizumab or ustekinumab. The study will recruit 40 outpatients at 2 Canadian healthcare centres at the University of Alberta Hospital (University of Alberta), and the Hamilton Health Sciences (McMaster University).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
FMT, Microbiome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
To maintain blinding, LFMT and placebo capsules will appear identical.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LFMT capsules + vedolizumab
Arm Type
Experimental
Arm Description
The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.
Arm Title
Placebo capsules + vedolizumab
Arm Type
Placebo Comparator
Arm Description
The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.
Arm Title
LFMT capsules + ustekinumab
Arm Type
Experimental
Arm Description
The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.
Arm Title
Placebo capsules + ustekinumab
Arm Type
Placebo Comparator
Arm Description
The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.
Intervention Type
Drug
Intervention Name(s)
Lyophilized fecal microbiota (LFMT)
Intervention Description
vedolizumab or ustekinumab + FMT vs placebo
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Proportion of participants with serious adverse events (SAEs) of interest up to week 8 in each group (ie vedolizumab with or without LFMT, ustekinumab with or without LFMT).
Description
SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Proportion of participants in each group with adverse events during the study up to week 24, including nausea, vomiting, abdominal pain, worsening diarrhea, constipation or fevers
Time Frame
24 weeks
Title
Proportion of participants who achieve clinical remission, defined as total Mayo score ≤ 2 with no individual subscore > 1, at week 8 and 24 in each group.
Time Frame
24 weeks
Title
Proportion of participants who achieve clinical response
Description
Defined as a reduction in the Mayo clinic score of ≥ 3 points and/ or ≥ 30% from baseline, with a decrease in the rectal bleeding subscore of ≥ 1 point or a subscore ≤ 1 at week 8 and 24 in each group
Time Frame
24 weeks
Title
Proportion of participants who achieve symptom remission, defined as partial Mayo score < 2 with no individual subscore > 1, at week 8 and 24 in each group
Time Frame
24 weeks
Title
Proportion of participants who achieve symptom response, defined as reduction in partial Mayo score ≥ 2 points from baseline and ≥ 30% from baseline and decrease in rectal bleeding score of ≥ 1point from baseline, at week 8 and 24 in each group
Time Frame
24 weeks
Title
Proportion of participants who achieve endoscopic improvement, defined as Mayo endoscopic subscore ≤1, at week 8 and 24 in each group
Time Frame
24 weeks
Title
Changes in partial Mayo score over time up to week 24 relative to baseline in each group
Time Frame
24 weeks
Title
Changes in quality of life, assessed by short IBD Questionnaire (sIBDQ), and work productivity, assessed by Work Productivity and Activity Impairment Questionnaire (WPAIQ), at week 8 and 24 relative to baseline in each group
Time Frame
24 weeks
Title
Changes in inflammatory markers (serum c-reactive protein (CRP) and fecal calprotectin) over time up to week 24 in each group
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Proportion of participants with Corticosteroid-free remission at week 8 and 24
Time Frame
24 weeks
Title
Time to clinical remission, clinical response, symptom remission and symptom response in each group
Time Frame
24 weeks
Title
Changes in stool microbiome at week 8 and 24 relative to baseline in each group
Time Frame
24 weeks
Title
Changes in stool microbiome at time of remission relative to baseline in each group
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age or older but less than 75 years of age Able to provide informed consent Established ulcerative colitis diagnosis determined by a physician through standard endoscopic and histologic criteria Active UC defined as total Mayo score between 6-12 AND Mayo endoscopic sub-score >1 with disease that extends 15 cm or more from the anal verge Selected by treating physician for initiation of biologic treatment with either vedolizumab or ustekinumab. Patients must be: Biologic naive; OR Have failed anti-TNF, anti-integrin, anti IL12/23 or oral small molecules Use of effective contraception method for women of childbearing potential for at least 4 weeks prior to receiving study treatment and for the duration of the trial Willing and able to comply with all required study procedures Exclusion Criteria: Severe UC requiring hospitalization Indeterminate colitis Evidence of or treatment for C difficile infection or other intestinal pathogen, including CMV, within 4 weeks prior to enrollment Evidence of toxic megacolon or gastrointestinal perforation on imaging Abdominal surgery within the past 60 days Neutropenia with absolute neutrophil count <0.5 x 109/L Peripheral white blood cell count > 35.0 x 109/L and fever (>38 degrees Celsius) Planned or actively taking another investigational product Uncontrolled medical conditions such as psychiatric disorders or substance abuse Severe underlying disease such that the patient is not expected to survive for at least 30 days Pregnant or lactating Unwilling to discontinue non-dietary probiotic Antibiotic use in the past 30 days or anticipated need for systemic antibiotic use during study FMT within 3 months prior to enrollment Use of the following medications: rectal/topical therapy within 2 weeks of screening cyclosporine, tacrolimus or thalidomide within 4 weeks of screening tofacitinib within 4 weeks of screening adalimumab or infliximab within 8 weeks of screening vedolizumab within 8 weeks of screening ustekinumab within 12 weeks of screening prednisone > 30 mg/d Investigator deems enrolment in the study is not in the best interest of the patient
Facility Information:
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2X8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dina Kao, MD
Phone
780 492 8307
Email
dkao@ualberta.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

LFMT vs Placebo in New Biologic Start for Ulcerative Colitis

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