This phase I trial studies how well fecal microbiota transplant and dietary fiber supplementation work in treating patients with gut graft versus host disease. Fecal microbiota transplant entails inoculating donor stool into a recipient's gastrointestinal tract. Changing the gut microbiome by fecal microbiota transplant and fiber supplementation may help treat gut graft versus host disease.
OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients receive upper FMT capsules orally (PO) over 5 days or via post-pyloric or nasogastric (NG) feeding tube over 2 days. ARM II: Patients undergo lower FMT via colonoscopy on day 0. ARM III: Patients receive upper FMT capsules PO over 5 days or via post-pyloric or NG feeding tube over 2 days. Patients also receive fiber supplementation PO or via post-pyloric or NG feeding tube from the first day of FMT administration and up to 6 weeks post FMT. ARM IV: Patients undergo lower FMT via colonoscopy on day 0. Patients also receive fiber supplementation PO or via post-pyloric or NG feeding tube from day 0 up to 6 weeks post FMT. Patients also undergo tissue, stool, stool swabs, and blood sample collection throughout the study. After completion of study treatment, patients are followed up for 365 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
Undergo lower FMT via colonoscopy
Given upper FMT PO or via post-pyloric or NG feeding tube
Undergo lower FMT via colonoscopy
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGBacterial composition of stool
Analyses will consist of summary statistics of the bacterial diversity in the microbiome (e.g., the alpha diversity, the abundance of bacterial species associated with protection from graft versus host disease \[GvHD\]).
Time frame: At baseline
Bacterial genes in stool
Specifically abundance of genes related to fiber fermentation and short chain fatty acids production metabolites in stool, specifically short chain fatty acids will be assessed.
Time frame: At baseline
Incidence of adverse events
Will by assessed by computing the total number of adverse events (AE)s and serious adverse events (SAE)s, the number per patient, and the number of patients with at least one event. The type of AE/SAE and whether the AE/SAE is related to the fecal microbiota transplant (FMT) or not will be tabulated. These summaries will be computed overall as well as by randomization arm and stratification factor (steroid-responsive, versus steroid-dependent or -refractory disease status). The odds will be compared of at least one SAE per patient by randomization arm and stratification factor using logistic regression with independent variables for route of FMT administration, fiber supplementation, and steroid-responsive, versus steroid-dependent or -refractory disease status. Interaction terms will be considered between these factors and may use exact or firth logistic regression in the event that some categories have zero patients with a SAE.
Time frame: Up to 3 years
Complete response (CR) after the initial FMT
Will be defined by stage 0 on the Modified Glucksberg GvHD scale, without abdominal pain or hematochezia. To account for variability in this measure, patient stool volume (inpatients only) and survey data (both inpatients and outpatients) from days 25-27 will be used to determine whether patients meet these criteria or not. Inpatients will be a compare measured stool volumes to those reported via survey, to assess how well the survey data may serve as a surrogate for stool volume. Subjects who die before day 28 will be counted as no CR. The number and proportion of patients with CR by steroid-responsive, versus steroid-dependent or -refractory disease status, and each randomization arm (route of FMT administration and receipt of fiber supplementation) as well as within combinations of these factors will be computed. To test for differences in CR by these factors, logistic regression models similar to those described above for SAE comparisons.
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Given dietary fiber supplementation PO or via post-pyloric or NG feeding tube
Ancillary studies
Undergo tissue, stool, stool swabs, and blood sample collection
Time frame: At day 28
CR or partial response (PR) after the initial FMT
Will be assessed by CR or PR at day 28 will use similar analysis methods as to the CR at day 28 outcome analysis.
Time frame: At day 28
Gut and overall GvHD grade
Will be assessed using the Modified Glucksberg scale measurements at baseline and throughout follow-up to summarize decrease in stool volume. For both of these ordinal outcomes (GvHD grade and Modified Glucksberg scale stage), descriptive statistics and graphical summaries to show changes over time by stratification factor and randomization arm. Generalized linear mixed effects models to test for differences in these outcomes by stratification factor and randomization arm.
Time frame: Up to 6 months
Six-month survival
Will be evaluated using Kaplan-Meier curves and Cox proportional hazards regression with independent variables for the steroid- responsive, versus steroid-dependent or - refractory disease and randomization arm as specified in previous models.
Time frame: At 6 months
Quality of life
Will be summarized at baseline and during study using descriptive statistics.
Time frame: Up to 3 years
Decrease in stool volume
Time frame: Up to 6 months
Levels of MAIT cells in the periphery
Will be assessed using plot cell counts and percentage of lymphocytes for MAIT cells over time to compare longitudinal patterns by study arm and stratification factor. Mann-Whitney tests will be used to evaluate differences in cell counts and percentage of lymphocytes for MAIT cells in recipients of upper versus lower FMT, and individuals who receive fiber supplementation versus those who do not at specific time points post-FMT. Linear mixed effects models may be used to test for differences in longitudinal patterns of these outcomes by randomization arm and stratification factor.
Time frame: Up to 6 months
Levels of Treg cells in the periphery
Will be assessed using plot cell counts and percentage of lymphocytes for Treg cells over time to compare longitudinal patterns by study arm and stratification factor. Mann-Whitney tests will be used to evaluate differences in cell counts and percentage of lymphocytes for Tregs in recipients of upper versus lower FMT, and individuals who receive fiber supplementation versus those who do not at specific time points post-FMT. Linear mixed effects models may be used to test for differences in longitudinal patterns of these outcomes by randomization arm and stratification factor.
Time frame: Up to 6 months