Inflammatory Bowel Diseases, Ulcerative Colitis
Conditions
Keywords
FMT, Fecal Microbiota Transplantation, Inflammatory Bowel Diseases
Brief summary
A double-blind, randomized, placebo-controlled clinical trial examining the efficacy and safety of Fecal Microbiota Transplantation (FMT) and high fiber supplementation in patients with active mild to moderate Ulcerative Colitis (UC). All enrolled subjects will provide serological, stool and mucosal specimen at each clinic visit to help further define the alterations in microbial profiles and immune cell function in response to psyllium fiber after FMT treatment.
Detailed description
This is a randomized, double-blind, placebo-controlled clinical trial with the following treatment assignments: 1. Investigational FMT (one-time) 1. Subject will blindly receive investigational FMT once at day 0 colonoscopy 2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy. 2. Investigational FMT (one-time) + Psyllium (2x/day for 8 weeks) 1. Subject will blindly receive investigational FMT once at day 0 colonoscopy 2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy. 3. Placebo FMT (one-time) +/- Psyllium (2x/day for 8 weeks) 1. Subject will blindly receive placebo FMT once at day 0 colonoscopy 2. Subjects in this group will blindly receive investigational FMP250 at week 8 by flexible sigmoidoscopy. Subjects will blindly receive the investigational or placebo FMP250 treatment if they meet all inclusion and exclusion criteria during the day 0 screening colonoscopy. Subjects will receive follow-up phone calls at day 1, week 2, week 6, and week 10 post-FMT and will return for clinic visits at week 4, week 8 and week 12 post-FMT. Stool and blood samples will be collected for research purposes from subjects at every clinic visit (Day 0 colonoscopy, Week 4, Week 8, and Week 12). Mucosal biopsies will also be taken during the initial colonoscopy, at day 0 and during the follow-up flexible sigmoidoscopy at week 8. At week 8 post-FMT, all subjects will be evaluated by flexible sigmoidoscopy. Subjects originally randomized into the placebo cohort at week 0 will receive investigational FMP250 by flexible sigmoidoscopy at week 8, and subjects originally randomized into the investigational cohort at week 0 will receive placebo FMP250 by flexible sigmoidoscopy at week 8. Lastly, all subjects will be contacted for follow-up phone calls every subsequent 6 months for the next year.
Interventions
DRUGFecal Microbiota Transplantation
The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8. Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery.
DIETARY_SUPPLEMENTPsyllium Husk Powder
All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy. Psyllium husk powder is the dried and powdered form of a psyllium seed coat.
Sponsors
Crohn's and Colitis Foundation
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blinded study
Intervention model description
Eligible subjects will be randomly assigned to one of the three (Placebo or Investigational FMT +/- Psyllium) treatment groups. A series of randomized blocks of 6-10 will be generated with a 1:1:1 allocation ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female ≥ 18 years of age. * Documentation of prior history of mild to moderate UC. * Endoscopy confirmed active UC ≥ 15 centimeters at week 0 screening colonoscopy. a. As defined by a total Mayo scoring of 4-10 with an endoscopic sub-score ≥ 1. * Patients must have a descending intact colon. * Patients taking steroid or biologic therapy must be on a stable dose for 4 weeks prior to screening and maintained throughout the trial. * Eligible patients willing to undergo screening testing prior to FMT to document baseline status: 1. Urine Testing 2. Blood Testing 3. Stool Testing * Patients must discontinue anti-rCDI antibiotics (e.g. vancomycin, fidaxomicin) 48 hours prior to FMT delivery procedure.
Exclusion criteria
* Biopsy proven Crohn's disease * UC patients with severe disease (defined as a total mayo score \>10) * Clinical complications requiring emergent management (e.g. stricture, bowel obstruction, perforation and/or abscess) * Concurrent C. difficile or other infections * Primary sclerosing cholangitis * Prior history of FMT * Treatment for malignancy within past 5 years * Active or latent tuberculosis * Clinically meaningful laboratory abnormalities 1. Hb: \< 8 2. ALT: greater than 3x the ULN (upper limit of normal) * History of anaphylactic reactions to food allergens or allergy to psyllium husk * Subject having any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response | Week 8 post-FMT | Clinical response at week 8 post-FMT, as defined by the reduction of the Mayo scoring system by \>3 points (+30% reduction) with an accompanying decrease in the sub-score for rectal bleeding of at least 1 point |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission | Week 8 post-FMT | Clinical remission at week 8 post-FMT, as defined by Mayo score ≤ 2 without any subscore \>1 |
| Endoscopic Response or Remission | Week 8 post-FMT | Endoscopic response or remission at week 8 post-FMT, as defined by a Mayo endoscopic sub-score 0-1 with at least a 1-point reduction from baseline or a Mayo endoscopic sub-score of 0 |
| Number of Treatment or Disease Related Adverse Events. | Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT | Adverse event counts are cumulative frequencies of adverse and severe adverse events assessed at Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational FMT Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy.
Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy.
Fecal Microbiota Transplantation: The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8.
Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery. | 9 |
| Investigational FMT + Psyllium Fiber Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy. They will also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks.
Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy.
Fecal Microbiota Transplantation: The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8.
Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery.
Psyllium Husk Powder: All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy.
Psyllium husk powder is the dried and powdered form of a psyllium seed coat. | 9 |
| Placebo FMT +/- Psyllium Fiber Participants will be blindly randomized to receive a single dose of placebo FMT during the week 0 colonoscopy. They may or may not also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks.
Additionally, participants will blindly receive a single dose of investigational FMT during the week 8 by flexible sigmoidoscopy.
Psyllium Husk Powder: All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy.
Psyllium husk powder is the dried and powdered form of a psyllium seed coat. | 9 |
| Total | 27 |
Baseline characteristics
| Characteristic | Investigational FMT | Investigational FMT + Psyllium Fiber | Placebo FMT +/- Psyllium Fiber | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 8 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 8 Participants | 25 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 9 participants | 27 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 4 / 9 | 7 / 9 | 6 / 9 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Clinical Response
Clinical response at week 8 post-FMT, as defined by the reduction of the Mayo scoring system by \>3 points (+30% reduction) with an accompanying decrease in the sub-score for rectal bleeding of at least 1 point
Time frame: Week 8 post-FMT
Population: Analysis will be performed based on intent to treat. Therefore, any subjects with missing primary endpoint data at week 8 will have their baseline Mayo score carried forward to remain the same for the week 8 primary endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational FMT | Clinical Response | 5 Participants |
| Investigational FMT + Psyllium Fiber | Clinical Response | 2 Participants |
| Placebo FMT +/- Psyllium Fiber | Clinical Response | 1 Participants |
Secondary
Clinical Remission
Clinical remission at week 8 post-FMT, as defined by Mayo score ≤ 2 without any subscore \>1
Time frame: Week 8 post-FMT
Population: Analysis will be performed based on intent to treat. Therefore, any subjects with missing data at week 8 will have their baseline Mayo score carried forward to remain the same for the evaluation of clinical remission at week 8.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational FMT | Clinical Remission | 3 Participants |
| Investigational FMT + Psyllium Fiber | Clinical Remission | 1 Participants |
| Placebo FMT +/- Psyllium Fiber | Clinical Remission | 0 Participants |
Secondary
Endoscopic Response or Remission
Endoscopic response or remission at week 8 post-FMT, as defined by a Mayo endoscopic sub-score 0-1 with at least a 1-point reduction from baseline or a Mayo endoscopic sub-score of 0
Time frame: Week 8 post-FMT
Population: Analysis will be performed based on intent to treat. Therefore, any subjects with missing data at week 8 will have their baseline Mayo score carried forward to remain the same for the evaluation of endoscopic response and remission at week 8.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational FMT | Endoscopic Response or Remission | 4 Participants |
| Investigational FMT + Psyllium Fiber | Endoscopic Response or Remission | 2 Participants |
| Placebo FMT +/- Psyllium Fiber | Endoscopic Response or Remission | 0 Participants |
Secondary
Number of Treatment or Disease Related Adverse Events.
Adverse event counts are cumulative frequencies of adverse and severe adverse events assessed at Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT.
Time frame: Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational FMT | Number of Treatment or Disease Related Adverse Events. | 21 Adverse and Severe Adverse Events |
| Investigational FMT + Psyllium Fiber | Number of Treatment or Disease Related Adverse Events. | 33 Adverse and Severe Adverse Events |
| Placebo FMT +/- Psyllium Fiber | Number of Treatment or Disease Related Adverse Events. | 20 Adverse and Severe Adverse Events |