Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT06254625 |
Other study ID # |
333-2023-AK |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
April 1, 2024 |
Est. completion date |
December 31, 2024 |
Study information
Verified date |
April 2024 |
Source |
Odense University Hospital |
Contact |
Camilla Thorndal Nielsen, Medical student |
Phone |
+45 65415190 |
Email |
Camilla.Thorndal.Nielsen[@]rsyd.dk |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to investigate the safety and effect of fecal microbiome
transplantation (FMT) in patients with a former episode of acute colonic diverticulitis. The
main question[s] it aims to answer are:
- Is FMT in patients with a former episode of acute colonic diverticulitis a safe
procedure without severe adverse events
- What is the impact of FMT on patient-reported outcomes and re-admission rate
Participants will be asked to:
- to ingest either 25-30 capsules with FMT or placebo capsules
- Fill-in GI-QLI questionnaire prior to treatment/placebo and 3 months post baseline
- Fill-in eating habit questionnaire
- deliver blood-and stool samples prior to treatment/placebo and 3 months post baseline
- In both the treatment and placebo group 5 patients will be offered sigmoideoscopy for
mucosal biopsies if it is more than 2 items]. If there is a comparison group:
Researchers will compare [insert groups] to see if [insert effects]
Description:
Colon diverticulosis (CD) is a prevalent condition, and its global incidence appears to be
rising due to the aging population and an increasing number of younger individuals affected.
Symptoms may encompass abdominal pain, changes in bowel habits, and bloating. The prevailing
hypothesis suggests that CD arises from chronic constipation, resulting in heightened
intraluminal pressure, colonic muscular hypertrophy, and mucosal herniation. However, the
etiology remains incompletely understood, involving complex interactions among genetic
factors, gut microbiota, and diet. The path from CD to diverticulitis is believed to involve
diverticular obstruction, alterations in the gut microbiome, local tissue ischemia, and
micro-perforations. Recent studies provide evidence supporting the role of altered colonic
microbiota in CD pathogenesis, showing compositional changes in the microbiome of inpatients
with acute diverticulitis (AD) characterized by decreased diversity and abundance of
commensal microbiota as compared to healthy controls.
Traditionally, diverticulitis has been treated with antibiotics due to its association with
bacterial overgrowth in the large intestine. However, prolonged antibiotic therapy has led to
complications, such as Clostridioides difficile infection (CDI). Currently, studies are
exploring the clinical evidence supporting the use of antibiotics for uncomplicated
diverticulitis.
Fecal microbiota transplantation (FMT) has emerged as a novel therapeutic approach for
recurrent CDI, involving the transfer of stool from healthy donors to the gastrointestinal
tract of a recipient/patient. FMT is considered a safe and effective strategy to restore a
healthy diversity of the gastrointestinal microbiota in patients with CDI. Furthermore,
systematic reviews have demonstrated positive responses of FMT in managing inflammatory bowel
disease (IBD), showcasing local therapeutic immune-modulating abilities.
Typically, patients with AD present with acute pain, tenderness in the left lower quadrant,
fever, and elevated infection parameters. AD severity is categorized as uncomplicated
diverticulitis or complicated diverticulitis, using the Hinchey classification. In Denmark,
the diagnosis of diverticulitis is confirmed with a CT scan during acute hospitalization.
While optical colonoscopy (OC) is rarely used for diagnostic purposes in the clinical setting
due to the risk of complications, patients are offered a follow-up OC after conservative AD
treatment, typically six weeks after inflammation resolution, to exclude malignancy.
Purpose The investigators aim to evaluate clinical and patient-reported efficacy, safety, and
impact on the colonic microbiome of one FMT or one placebo-FMT administered via capsules in
patients with diverticulitis.
Study Design The study is designed as a randomized controlled trial (RCT) with the primary
objective of investigating the feasibility, tolerability and safety of FMT in patients with
acute uncomplicated diverticulitis at Odense University Hospital (Odense/Svendborg).
Patient selection: The study population will consist of patients admitted to Odense
University Hospital Patients with acute uncomplicated diverticulitis. Eligible patients will
be identified during hospital admission and assessed for inclusion in the study. To be
eligible, the diverticulitis in the patient must be acute uncomplicated, as confirmed by CT
scan. After hospital discharge, eligible patients will be offered the opportunity to
participate in the study.
Informed Consent: All prospective participants will be required to provide both verbal and
written informed consent before they are included in the study. Invitees will also be
informed that they have the option to decline FMT treatment at the day of capsule
administration. If the patient chooses to refuse participation, they will be offered no
further treatment, as planned at hospital discharge.
Sample Size and Randomization: The study will include a total of 40 patients, all of whom
have CT-confirmed diverticulitis. These patients will be randomized 1:1 into two study arms.
- Active Treatment Group: This group will comprise 20 patients who will receive FMT in
capsule form.
- Control Group: The control group will also consist of 20 patients who will receive
placebo treatment also in capsule form.
Blinding: The study will be conducted in a double-blind manner to minimize bias. Neither the
personnel nor the patients will be aware of whether FMT is administered or not in the
capsules. A designated coordinator will coordinate with clinical immunological department,
which will then deliver the products, along with the transplantation journal (whether FMT or
placebo), to the core department of the patients.
In summary, this study employs a RCT design to assess the feasibility, tolerability, and
safety of FMT in patients with acute uncomplicated diverticulitis. A total of 40 patients
will be enrolled and randomly assigned to either the active treatment group (FMT) or the
control group (placebo). The study will be blinded to ensure impartial evaluation of
outcomes. Eligible patients will provide informed consent before participating in the study.
Endpoints
- Primary efficacy endpoint: Proportion of patients treated with antibiotics within 3
months following FMT comparing FMT and placebo.
- Primary safety endpoint: Patient safety monitored by a) number of re-admissions, and b)
number of adverse events within 3 months of FMT.
- Secondary endpoints: Change from baseline to 3 months in the GI-QLI questionnaire.
Change from baseline to 3 months in: fecal bacteria composition and metabolism;
intestinal permeability (measured by specific markers in plasma); plasma and fecal
calprotectin; specific circulating inflammatory markers (ie, cytokines, adipokines and
chemokines); and macroscopic and microscopic inflammatory changes of the colonic mucosa.
Recruitment of patients The recruitment of patients will occur within the Surgical Department
or Emergency department at Odense University Hospital (Odense/Svendborg). Patient enrollment
takes place during hospital admission in conjunction with their acute diverticulitis episode.
The first contact with the patients is initiated by the attending physician following a CT
scan confirming uncomplicated diverticulitis and when the patient's condition stabilizes with
conservative treatment.
Upon informing the patient that they have uncomplicated diverticulitis and do not need or
will get any further treatment, the attending doctor will also provide information about the
project, including an explanation of FMT is and its former use. Subsequently, the attending
doctor will make a referral to either Camilla Thorndal Nielsen or Thomas Bjørsum-Meyer, who
will then contact the patient to provide verbal information with the aim of facilitating
enrollment during the hospital stay. In cases where the patient has not been informed during
admission, a meeting will be offered 14 days after discharge. Furthermore, the patients will
have the opportunity to undergo a sigmoidoscopy, the primary purpose of which is to obtain
biopsies for examination of the colonic mucosa. This will be performed at baseline (prior to
FMT administration) and at 3 months after. To consent to this, there will be a checkbox to
mark on the consent form.
Patients will be informed about the right for the presence of a layman representative during
discussions and their right to a period of reflection within an undisturbed room prior to
making a decision regarding participation. Furthermore, patients will be presented with the
option of physical or online follow-up consultation with either Thomas Bjørsum-Meyer or
Camilla Thorndal Nielsen, scheduled for 14 days after discharge. To ensure clarity, patients
will be provided with the pamphlets titled "Forsøgspersoners rettigheder i et
sundhedsvidenskabeligt forskningsprojekt" and "Før du besluttter dig", as well as our
Participant Information on the trial. Written consent will be obtained prior to the patient's
discharge. Alternatively, patients may provide written consent for participation during the
consultation scheduled 14 days after discharge. Failure to receive a response from a patient
regarding their participation within 14 days following hospital discharge, will render them
ineligible for participation.
The Study Procedure At the out-patient consultation 14 days after hospital discharge the
patients will receive a fecal sampling and be instructed to fill 3-5 fecal samples. If the
patient has consented to the sigmoidoscopy they will be instructed to fill the fecal samples
BEFORE they start the regimen of bowel cleansing. Before the FMT procedure they will be asked
to fill in 2 questionnaires to report on their symptoms: the Eating Habits Questionnaire and
the Gastrointestinal Quality of Life (GI-QLI). Both questionnaires will be sent in a digital
mail via e-boks or by mail. The GI-QLI is a 36-item multidimensional scale covering symptoms,
and physical, emotional, and social dysfunction relating to gastrointestinal diseases or
their treatments. It is an appropriate and validated tool to assess health-related quality of
life in clinical studies in patients with gastrointestinal disease. Each of the 36 items are
scored on a 5-point Likert scale and summed to get overall GI-QLI score. The Eating Habits
questionnaire covers the patient's average eating habits in the last month.
At the day FMT treatment, they will bring the fecal samples to the clinic. In the clinic on
the day of the FMT treatment they will have blood samples taken. The intervention will be
conducted at the patient's core department: the surgical department at Odense University
Hospital (Odense/Svendborg/Nyborg). If they have agreed to a sigmoidoscopy, there will be
taken brush biopsies of the mucosa, in both the treatment group and the placebo group.
Three months post baseline the patients will receive the QI-GLI questionnaire digitally
again, as well as another fecal sampling set by mail, which they will be asked to bring when
they have their blood samples taken for the second time and, for those it may be relevant
undergo the second sigmoidoscopy.
The investigators will monitor and report safety outcomes by re-admissions, adverse events
and need for antibiotics, during the whole study period.
Randomization The randomization will be managed by randomization tool in Open REDCap. The
patients, care providers, and outcome assessors will remain unaware of the group assignments,
and only de-identified codes will be used to link participants to their data during the study
to maintain their confidentiality. In case of exceptional circumstances when knowledge of the
treatment allocation is essential for further management of the patient, the trial secretary
will reveal the assigned intervention to the treating doctor. However, patients, trial care
providers and outcome assessors will remain blinded as far as possible. Cases of unblinding
will be registered and reported. The study will be terminated when 40 patients have been
included in total, which is anticipated to be achieved within a 6-months period.
The FMT procedure Use of capsule-based fecal microbiota transplantation has been shown to be
clinically effective approach to restore intestinal microbiota composition and is now the
preferred form of administration. This non-invasive oral delivery provides an easy route of
administration and a newfound flexibility for clinicans and patients. 25-30 capsules are
ingested with apple juice or coca cola light, and the patient is observed for 30-60 minutes
before they are allowed to go home. The capsules are to be ingested within 4 hours of
thawing. Each transplant, comprising 25-30 capsules, contain 50 g of feces originating from
one donor. The placebo group receives placebo capsules. The patients will only receive the
FMT or placebo capsules once.
Collecting of biological material Fecal samples: The patient will collect 5 stool samples
consisting of 1g each. The same material for biobanking will be collected at both baseline
and 3 months follow-up. The investigators will investigate the fecal microbioal composition
(i.e, bacteria, virus, fungi, and archea) and microbial activity using metagenomics/16S,
culturomics, proteomics, and metabolomis. Fecal samples will also be taken if the patient is
admitted in need for antibiotics, prior to the treatment.
Blood samples: At baseline the patient will have 5 blood tests taken, and this will again be
done at the 3 months follow-up. Markers of intestinal permeability will be investigated such
as plasma zonulin, zonulin-related protein, calprotectin, I-FABP, CD14, and LPS. Furthermore,
Analyses of inflammation-related plasma proteins using the Olink 92 inflammation panel (link)
or a similar protein assay will be conducted.
Brush biopsy: During the baseline sigmoidoscopy and the second one, a brush biopsy (0.1g /
1x1 mm) will be obtained from the gastrointestinal mucosa of the patient's colon. The purpose
of this procedure is to examine the microenvironment in the diverticula, focusing on
inflammation or other microbiological abnormalities. Both paraffin-fixed tissue for
immunohistochemistry and tissue stored in RNALater for proteomics will be collected.
All brush biopsies, blood samples and fecal samples will be stored in a research biobank for
current and future research with the subject's consent. Four biobanks (A, B, C and D) will be
established:
A. Blood samples biobanking (both patients and donors)
- 5 x Plasma-EDTA 1 ml (2.0 ml Sarstedt tubes)
B. Fecal samples biobanking (patients)
- 5 x 1 g stool from each donation
- 1 x brush biopsy of gastrointestinal mucosa (0.1 g / 1x1 mm)
C. Screening samples (donor)
- 2 x 7 blood samples (4 ml)
- 2 x 1 fecal sample (15 g)
- 2 x 1 urine sample (5 ml)
- 5 x swab SARS CoV2 PCR test
D. Fecal samples biobanking (donors)
- 3 x 1 g stool from each donation
- 3 x 1 g FMT transplant from each donation
At the end of the project, any additional material will continue to be stored in their
respective biobanks, for future research, if the subjects consent to this.
Recruitment of donors The recruitment of donors will occur at the Blood bank at Odense
University Hospital, Stærmosegårdsvej 6, 5230 Odense M. Donors will be sourced from active
members of the Danish blood donor corps. The recruitment of stool donors will take place
through discussions and material exchanges with the Blood Bank personnel during their blood
donations appointments.
When donors express interest in the project, comprehensive verbal information about the
project is provided by a medical doctor affiliated the Blood Bank. Donors are made aware that
they have the option to bring a layperson representative and are entitled to a period of
reflection. In additions, they will be encouraged to read the pamphlets titled
"Forsøgspersoners rettigheder i et sundhedsvidenskabeligt forskningsprojekt" and "Før du
besluttter dig". The reflection period, starting from the conveyance of verbal information
and extending to the procurement of informed consent, will span 1 week. Subsequently, our
written participant information document will be provided to the selected donors.
Stool donors: The stool donor corps will consist of 2 anonymous (to the recipient) donors who
must be healthy as assessed by screening questionnaire and be active members of the Danish
blood donor corps, age 25-55 years, body mass index between 18.5 and 25 kg/m2 and an average
alcohol intake <7 (women) and <14 (men) units per week. No alcohol intake within a week of
donation is allowed, and no systemic medication including antibiotics and NSAIDs 6 months
prior to the donation are allowed. The donor must eat a balanced diet (no extreme low-calorie
or high-calorie diets) and must not be in a stressful life period. Before joining the stool
donor corps, each potential donor will go through a screening process including stool
analyses for fecal calprotectin and enteric pathogens (Aeromonas, Campylobacter, C.
difficile, diarrhoeagenic Escherichia coli, Salmonella, Shigella, Vibrio, Yersinia
enterocolitica and multidrug-resistant bacteria), parasites including microscopy of ova and
cysts, Entamoeba histolytica/dispar (DNA), Cryptosporidium (DNA) and Giardia (DNA),
sapo-virus (RNA), rotavirus (RNA), human astrovirus (RNA), human adenoviruses (DNA) and
noroviruses (RNA), a Helicobacter pylori antigen test, blood test for CRP) (acceptable level:
<6.0 mg/L), white blood cell count (acceptable range: 3.50-8.8x10^9/L), hemoglobin
(acceptable range: 8.3-10.5 mmol/L), albumin (acceptable range: 36-50g/L), alanine
aminotransferase (acceptable range:10-70 U/L), estimated glomerular filtration rate
(acceptable range:>59 mL/min) and coeliac disease, and blood test for infectious agents
including current infection with Epstein-Barr virus (IgM) and cytomegalovirus (IgM),
hepatitis A, B, C and E, tuberculosis (QuantiFERON TB-Gold test), syphilis, HIV (ab HTLV1/2),
E. histolytica (antibodies) and Strongyloides (antibodies), and a urine test for Chlamydia
Trachomatis and Neisseria gonorrhoeae (DNA/RNA). After passing the screening tests, the donor
will donate stool for the next month after which, the donor will have to pass the screening
program once more before the stool can be released for transplantation.
Preparing the FMT suspension: Donors will collect stool at home and transport it in a cooling
bag to the study within 1 hour. Stool will be sieved to remove particulate material, followed
by dilution in sterile saline (0.9% NaCl) and 10% glycerol, The FMT suspension will be stored
at -80 degree C until use. On the day of the FMT transplantation, the transplant suspension
(250 mL) will be thawed to 37degree C and subsequently apportioned into five 50 mL syringes.
When preparing the final FMT solution, it's sought to split pools from the same batch,
however if there are less than five splits remaining from the same donation date, it is
allowed to split from the same donor collected on different dates. The optimal storage life
for frozen stool product has yet to be clarified, but it is widely accepted that the
transplant material can be stored at -80 degree C for 2 years, and most likely much longer.
Information from patient files Departments including patients will contact the investigator
and co-investigator, when they find a patient, which they deem suitable for the study. The
investigator and co-investigator will then approach these patients, with information about
the project.
Information that is extracted before consent to participate and forwarded to the researcher:
- Personal registration number (CPR)
- Age
- Gender
- Earlier hospitalization, especially with diverticulitis
- Earlier treatment with antibiotics within 12 months prior to inclusion
- Comorbidities and diseases, and other, which could be reason for exclusion.
- CT findings
- Symptoms at admission with acute diverticulitis
Information that is extracted after consent to participate, which gives project manager,
sponsors and sponsor represents, as well as control authorities direct access to obtain
information in patient journals.
- Symptoms after discharge (if any)
- Intake of antibiotics
- Readmission
- Patient file on sigmoidoscopy procedure.
- Symptoms and possible readmission after treatment
- Patient reported earlier antibiotic use. Data is used if patients' needs to be excluded
while the project is running.
Management of patient information in the project Data on participants will be collected from
electronic patient files and questionnaires. Only relevant information for conducting the
study is extracted. Data will be entered via a secure web-based electronic clinical report
form into a central RedCap database hosted by Odense Patient data Explorative Network at
Odense University Hospital. Data obtained during the clinical examination will be entered
directly into the database. Also, patient questionnaires will be filled out directly into the
database. Access to the study data will be restricted, and a password system will be used to
control access. All information about the patients' health and other private matters is
covered by confidentiality, as well as information about biobank materials. The information
will continue to be so after the project ends, this also includes material that will continue
to be stored in one of the research biobanks. Gathered information on participants is
protected according to the "Legislation on the Processing of Personal Data" and "Danish
Health Care Act". The authorization from Danish Data Protection Agency will be secured.
Risks and side effects The treatment that is being offered here, is identical with the
treatment that is given as routine to patients with CDI. It is the same product, amount of
the product and procedure. This has run routinely at Odense University Hospital for the last
5 years since 2017. The most frequently reported short-term minor adverse events (AEs)
related to FMT are vomiting, mild diarrhea, abdominal cramping, transient fever, and elevated
CRP. The possible serious short-term AE's related to the procedure are rare and primarily not
related to the administration of FMT. These include complications of the endoscopy, such as
perforation and bleeding, and complications related to the sedation, such as aspiration.
A recent systematic review has investigated the adverse events of FMT and found a total
incidence rate of 28.5%, in 50 relevant studies with a total of 1089 patients. In 5 out of 42
publications the events were definitely related to the FMT procedure, but in the remaining 38
they were described as probably related. The most common FMT AE was abdominal discomfort and
reported in 19 publications. The incidences of serious adverse events (SAEs) for FMT were
2.0% and 6.1% for upper and lower gastrointestinal routes, respectively. The SAEs that
possibly were related to FMT included infections (0.7%), IBD flare (0.6%), death (0.3%),
autoimmune disease and FMT procedure-related injury.
Although most of the knowledge on FMT related AEs are from patients who have suffered from
CDI and/or IBD, these findings request caution when performing FMT. However, FMT is in
general considered safe, especially with a strict screening of donors, and even elderly
patients with poor medical condition as well as immunosuppressed patients have been proven to
tolerate the procedure well.
In the present study, the investigators will carefully monitor and evaluate safety by means
of open assessment of adverse events. All reported or observed adverse events are recorded by
the investigators and will be monitored until resolution, stabilization or until it has been
shown that the study intervention is not the cause. The National Cancer Institute Common
Terminology Criteria for Adverse Events V.4.03 (NIH publication #09-7473) will be used to
grade the severity of AEs. Gastrointestinal side effects (nausea, vomiting, abdominal pain,
number of stools per week, stool type (Bristol Stool Chart) blood or mucus in stool) will be
registered by the patients once a week for the first month following the randomized
intervention. Subject incidence rates of all treatment-emergent AEs will be tabulated by
system organ class and preferred term. Tables of fatal AEs, severe AEs, AEs leading to
withdrawal from study and significant treatment-emergent AEs, will also be provided.
Statistical considerations When designing this trial, no prior data for FMT efficacy in
patients with diverticulitis were available. However, the investigators found it reasonable
to assume that if patients with acute uncomplicated diverticulitis should be willing to
receive FMT as a future standardized treatment, the procedure should at least provide an
effect size well beyond a moderate effect size. A smaller group of patients has been chosen,
since this is a pilot study, and it is not known how the patients with diverticulitis will
respond to the treatment with FMT.
Statistical methods The full analysis set will consist of all randomized participants, which
will be analyzed according to their randomized treatment group, so the participants allocated
to a treatment group will be followed up, assessed, and analyzed as members of that group,
irrespective of their compliance to the planned treatment (intention-to-treat principle). The
safety analysis set will include all patients who were randomly assigned to a study group and
has exposure to a transplant (independent of group). Descriptive statistics will be provided
for demographics and baseline characteristics. The summary statistics of continuous variables
will include N, mean, SD, median, interquartile range and range. All summaries presenting
frequencies and incidences will include counts, percentages, and the total number of
participants in the corresponding arm.
Ethics and dissemination This study is designed as a proof-of-concept clinical trial and will
be performed in agreement with Good Clinical Practice (GCP) standards, and in accordance with
the ethical standards of the responsible committee on human experimentation (institutional
and national) and with the Helsinki Declaration (64th, 2013). The trial will be started after
the regional ethics committee and the Data Protection Agency has approved the protocol. Data
will be handled according to the General Data Protection Regulation (GDPR) and the Data
Protection Act.
The Danish Health and Medicines Authority does not classify the FMT procedure as a medical
intervention and has had no objection to the use of FMT for this study and patient category.
Thus, no GCP auditing is legally required. A report describing any potential side effects and
AEs will be submitted to the Ethics Committee yearly. Suspected Unexpected Serious Adverse
Reactions will be reported to the Ethics Committee within 7 days. Based on these reports, the
Ethics committee can determine to terminate the trial early. The Danish Patient Compensation
Association provides compensations for patients injured in connection to medical clinical
trials. Although the Danish Health Authorities, for the time being, do not classify donor
fecal microbiota as tissue, all steps of the stool donor recruitment, stool donation and FMT
preparation will be in accordance with the Danish Tissue Law to ensure that the quality and
safety standards laid down in the Danish Legislation BEK nr 764 of 26 May 2015 (implementing
Directive 2004/23/EC) are met. Stool donors will be recruited from the South Danish
Transfusion Service & Tissue Centre, Department of Clinical Immunology, Odense University
Hospital, and they will be carefully screened for potentially transmissible infections and
other conditions associated with gut microbiota function before their stool can be released
for FMT. Being a stool donor is voluntary, and no compensation fee will be given.
Furthermore, to ensure donor traceability, each patient in the active treatment arm will only
receive microbiota from one donor. Also, frozen stool products will be clearly labelled with
a unique donation code based on the ISBT 128 coding and labelling system, and the release of
the final product will adhere to the standards for tissue and blood donation.
Due to uncomplicated diverticulitis being a common disease, with no treatment with great
clinical evidence, the identification of new treatment modalities is essential to help the
physician. All patients with acute uncomplicated diverticulitis, who are participating in
this study, would not receive any treatment, and therefore the patient population would
benefit greatly from new treatment options. The trial will be registered at
ClinicalTrials.gov, and important protocol modifications will be updated here. Dissemination
will occur through publications in international peer-reviewed journal(s). Positive as well
as negative results will be published. The investigators plan to publish the clinical
findings (primary and secondary endpoints) in one publication with CN as first author and TB
as last author. The tertiary endpoints will be published separately in one or more
publications.
Economics Initiative for the study was taken by Thomas Bjørsum-Meyer. The costs of the study
will be covered by OUH, Region of Southern Denmark and external funds. No funds have yet been
granted or applied for. The grants will cover the costs of establishing and maintaining the 4
research biobanks, practical costs (i.e. mail services), secretary, as well as the costs of
blood samples, stool samples and colonic mucosa biopsies and the FMT procedure. The Trial
Manager has no financial affiliation with study subjects or other interests in the study.
Funding is administered by an account subject to public audit.