In the last decades fecal microbiota transplantation (FMT) has been established as a
highly effective option recurrent Clostridioides difficile infection (rCDI) treatment,
with a success rate of nearly 90%. For this reason, it is recommended by international
guidelines as a treatment option for this indication in clinical practice.
Recently, a considerable body of evidence supports FMT as an effective and safe treatment
in patients affected by Ulcerative Colitis (UC). In a recent meta-analysis of 324
subjects with UC, 30.4% of patients achieved both clinical and endoscopic remission after
FMT compared to placebo (9.8%, P<0.00001). However, among the various published trials
there is a fair variability in terms of methods and results, which are not comparable to
those obtained in the rCDI.
Nowadays, one of the most critical factors involved in the effectiveness of FMT in UC
patients is the choice of the donor. In addition, several studies have shown that some
donors have been associated with a higher clinical response rate than others. This
hypothesis has been demonstrated in patients affected by irritable bowel syndrome, in
which the use of a super-donor (a healthy person who has the predictive clinical and
lifestyle characteristics of a healthy microbiota, and with a microbial profile
associated with favorable clinical conditions) resulted in significantly higher clinical
efficacy rates than placebo, similar to those obtained in rCDI (89%).
Currently, studies that explored the efficacy of the superdonor FMT in UC patients are
not yet available.
The extended aims of this study are:
To compare the efficacy of superdonor FMT and placebo FMT in treating
mild-to-moderate Ulcerative Colitis.
To investigate changes in gut microbiome after treatments
To investigate changes in serum cytokines after treatments
To investigate changes in disease activity, investigated by the use of partial mayo
score, after treatments.
The investigators will carry out a single-centre double blind, placebo-controlled,
randomized clinical trial of super - donor FMT vs placebo FMT in patients with
mild-to-moderate UC Patients will be recruited among those referred to the
gastroenterology unit of the Fondazione Policlinico Universitario "A. Gemelli". Patients
with all inclusion criteria and none of the exclusion criteria (detailed in the specific
section of this website) will be considered for this study.
Before randomization, demographic data will be collected by the gastroenterology staff.
Moreover, patients will be requested to give stool samples to be collected in a sterile,
sealed container and stored at -80°C for metagenomic assessment of gut microbiome by the
microbiology staff. Additionally, a blood sample will be collect for cytokine
immunoassays.
After baseline assessments, patients will be randomly assigned to one of the following
treatment arms:
Donor FMT (D-FMT)
Placebo FMT (P-FMT) Patients in both groups will undergo three FMT procedure. Each
patient in the D-FMT group will receive feces from one single donor. Placebo FMT
will be made of 250 mL water for colonoscopy or using empty capsules. The selection
of stool donors will be performed by the gastroenterology staff following protocols
previously recommended by international guidelines and according the new
recommendation imposed by the reorganization of fecal microbiota transplant during
the COVID-19 pandemic. The assignment of fecal infusates from healthy donors to
patients will be done randomly, without any specific recipient-donor match, as this
is not recommended by international guidelines All fecal infusates and capsules will
be manufactured in the microbiology unit of our hospital. Only frozen feces will be
used. Preparation of frozen feces will follow protocols from international
guidelines. Patients in both groups will undergo the first infusion by colonoscopy.
Then, patients will receive frozen fecal capsules ( 15 capsules b.i.d.) at 3 and 7
days after the first FMT.
Furthermore, patients in the D-FMT group receive a pre-conditioning with vancomycin and
neomycin+bacitracin for 3 days, because published data from our group show that pre-FMT
antibiotics are associated with higher rates of microbial engraftment rates and increased
clinical response regardless of the disease.
Patients of the P-FMT group will receive a pre-conditioning with placebo at the same
dose.
Follow-up visits will be performed by physicians from the gastroenterology unit. All
patients will be followed up for 2 months after the end of treatments. Follow-up visits
will be scheduled at week 1, week 4, and week 8, after the end of treatments.
At each visit the following assessments will be performed: 1) collection of stool samples
for microbiome analysis; 2) collection of blood sample for cytokine immunoassay; 3)
record of adverse events. Unscheduled follow-up visits will be offered if requested by
the patients.
Study Outcomes are detailed in the specific section of this website. The statistical
analysis will be performed both on an intention-to-treat and per-protocol basis.
Differences among groups will be assessed with a two tailed Wilcoxon-rank sum test for
continuous data and with Fisher's exact probability test (using two-tailed P-values) for
categorical data. Differences in cure percentages will be determined with Fisher's exact
test (with two-tailed P values). Microbiome analysis will be performed with shotgun
sequencing techniques. For microbiome analysis statistical differences between group
means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through the R
statistical software package (R Core Team, Vienna, Austria).