Clinical trial NCT05067595: Fecal Microbiota Transplant and Dietary Fiber Supplementation for the Treatment of Gut Graft Versus Host Disease
Official title: A Randomized, Controlled, Phase I Study of Fecal Microbiota Transplant and Dietary Fiber Supplementation in Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Intestinal Graft Versus Host Disease
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-10-05
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* History of allogeneic hematopoietic stem cell transplant in the past 365 days
* Post-engraftment, defined by time period following three consecutive days of sustained neutrophil engraftment with an absolute neutrophil count of at least 500 cells/mm\^1
* Mild to severe acute GI GvHD, at least stage 1, as measured by one of the following:

  * Modified Glucksberg criteria for GI GvHD averaged over 3 consecutive days and without another explanation for diarrhea such as laxative use or infection. In patients who have already had GI biopsy, biopsy histology must be compatible with GVHD, although biopsy is not required
  * Biopsy evidence of GI GVHD in the upper or lower GI tract

Exclusion Criteria:

* History of previous serious adverse events associated with FMT
* History of bowel perforation in the last 90 days
* History of gastrointestinal resection in the last 90 days
* History of intestinal obstruction in the last 90 days
* History of diverticulitis in the last 90 days
* History of celiac disease confirmed by serologic testing or small bowel biopsy
* History of severe dietary allergy as designated by World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System grade 2 or more
* Subjects who are cytomegalovirus (CMV) seronegative at the time of enrollment as indicated by clinical testing unless the fecal microbiota transplant (FMT) donor is CMV seronegative with negative plasma polymerase chain reaction (PCR) assays for CMV.
* Known allergies to loperamide, sodium chloride, glycerol, theobroma oil, hide bovine gelatin, sodium lauryl sulfate, colorants FD\&C, titanium dioxide, polyethylene glycol, sodium sulfate, sodium bicarbonate, sodium phosphate, benzalkonium chloride, disodium EDTA or potassium chloride.
* Currently pregnant, planning to become pregnant or breastfeeding during the study period. Women of childbearing potential (those who are not post-menopausal or post-hysterectomy) must be negative for pregnancy per urine pregnancy test at enrollment
* Individuals with the ability to conceive children who are not willing to abstain from sexual activity or use an effective form of birth control during the duration of the study
* Unwilling or unable to participate in study procedures including oral intake of FMT, colonoscopy, fiber supplementation, collection of stool samples and completion study surveys
* Cannot reasonably and safely participate in the study in the opinion of the investigators

Primary outcomes:
measure: Bacterial composition of stool
timeFrame: At baseline
measure: Bacterial genes in stool
timeFrame: At baseline
measure: Incidence of adverse events
timeFrame: Up to 3 years
Secondary outcomes:
measure: Complete response (CR) after the initial FMT
timeFrame: At day 28
measure: CR or partial response (PR) after the initial FMT
timeFrame: At day 28
measure: Gut and overall GvHD grade
timeFrame: Up to 6 months
measure: Six-month survival
timeFrame: At 6 months
measure: Quality of life
timeFrame: Up to 3 years
measure: Decrease in stool volume
timeFrame: Up to 6 months
measure: Levels of MAIT cells in the periphery
timeFrame: Up to 6 months
measure: Levels of Treg cells in the periphery
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: David Fredricks
role: PRINCIPAL_INVESTIGATOR
References: