Condition category
Digestive System
Date applied
11/07/2018
Date assigned
23/07/2018
Last edited
13/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Cancers of the blood, such as acute leukemia, can be treated through transplantation of stem cells from healthy donors. Because stem cells can develop into different types of cells, transplantation leads to development of a new immune system derived from the donor stem cells, which can then respond to the tumor cells and clear the tumor.
However, the new, donor immune system can sometimes respond to healthy tissue in the patient, which causes ‘graft versus host disease’ (GvHD). This can often occur in the intestines.
In healthy patients, the intestines have microbes that help to keep it healthy (gut microbiota). However, in patients with stem cell transplants, especially those who develop GvHD as a result, this damages that normal, healthy gut microbiota. Restoring a healthy gut microbiome could therefore cure GvHD.
One method of restoring a healthy gut microbiome is through fecal transplantation from people with healthy gut microbiota. We aimed to determine whether transplantation of healthy feces into the intestine of GvHD patients could cure GvHD and restore a healthy gut microbiome.

Who can participate?
Stem cell transplant patients aged 18 or older with intestinal GvHD that did not respond to corticosteroid treatment

What does the study involve?
Participants will receive a fecal microbiota transplant, donated from healthy volunteers on the same day, into the upper intestine using a nasogastric tube.

What are the possible benefits and risks of participating?
The possible benefit to participants of taking part is that FMT can result in a reduction in symptoms of GvHD. The possible risk to participants of taking part is that due to their intestinal inflammation, bacteria transplanted into the gut may be able to relocate into the blood stream, which could cause infection.

Where is the study run from?
Amsterdam University Medical Centers location AMC, Amsterdam, Netherlands

When is the study starting and how long is it expected to run for?
July 2015 to January 2019

Who is funding the study?
1. Netherlands Organisation for Scientific Research (Netherlands)
2. Landsteiner Foundation for Blood Research (Netherlands)
3. AMC Foundation (Netherlands)

Who is the main contact?
Dr M.D. Hazenburg
m.d.hazenburg@amc.uva.nl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mette Hazenberg

ORCID ID

Contact details

Amsterdam UMC
locatin AMC
Meibergdreef 9
Amsterdam
1105AZ
Netherlands
+31 20 566 5785
m.d.hazenberg@amc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

FARAH trial

Study information

Scientific title

FARAH study: Fecal trAnsplantation to Reduce therapy-refractory graft versus host
disease in Allogeneic Hematopoietic stem cell transplantation

Acronym

FARAH

Study hypothesis

Steroid-refractory or steroid-dependent GvHD can be treated by infusion of healthy feces via duodenal tube

Ethics approval

Medical ethics committee of the Academic Medical Center (AMC), 07/07/2016, NL55067.018.15, 2016_003#B2016460

Study design

Interventional single-armed non-randomised pilot study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details te request participant information sheet

Condition

Graft versus host disease of the intestine (GvHD)

Intervention

Healthy volunteers (male and female, aged less than 60 years, Western diet) were used as donors for FMT (fecal microbiota transplantation) and received a bowel lavage with 1 litre of macrogol solution (Klean-Prep/Moviprep/Norgine) at least two hours before FMT. Donor feces was collected on the day of transplantation and immediately processed by dilution with sterile saline (0.9%), stirring and filtration to obtain a fecal suspension of 300-500 ml. This solution was then administered to participants through a nasoduodenal tube within 6 hours after donor feces collection.
After FMT, patients are seen by their transplantation hematologist at a weekly interval during the first 4 weeks after FMT. During tapering of immunosuppressants, patients are seen weekly or biweekly, depending on the clinical situation. A significant number of patients will be admitted to the hospital during at least the first 4-6 weeks after FMT, where they will be taken care of by the ward hematologist.

Intervention type

Biological/Vaccine

Phase

Drug names

Primary outcome measure

1. Response to treatment measured by stool frequency and volume at 7 days, 28 days, 3 months and 6 months after FMT
2. Complete response to treatment defined as complete resolution of GvHD symptoms 4 weeks after FMT. Participants were classified as CR/sf (complete responders with secondary failure) or NR (non-responders, if there was no improvement in clinical grade or follow-up time was too short to assess the effect of FMT). This is self-reported (participants keep a defecation diary) and is assessed by a physician.

Secondary outcome measures

1. Normalisation of gut microbiome diversity, measured by 16S sequencing of microbiome diversity in stool at 1, 4, 12 and 24 weeks after FMT
2. Changes in inflammatory markers in blood and affected tissues, measured using C-reactive protein, immune subsets (T cells, B cells, innate lymphoid cells), their activation status and pro-inflammatory cytokines in the blood at 1, 4, 12 and 24 weeks after FMT. At 3 and 6 months after FMT, colon biopsies will be taken to investigate immune subsets and infiltration of inflammatory cells to this region using immunohistochemistry
3. Total number and severity of infections will be assessed using patients' medical charts
4. Total duration of hospital stays and readmissions will be assessed using patient's medical charts

Overall trial start date

01/07/2015

Overall trial end date

15/01/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Steroid-refractory or steroid-dependent graft versus host disease of the intestine
2. Aged 18 years or older

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

15

Participant exclusion criteria

1. Unable to provide informed consent

The use of immunosuppressive therapy and/or concurrent (systemic) infection does not exclude patients from participation in the study.

Recruitment start date

06/09/2016

Recruitment end date

17/05/2018

Locations

Countries of recruitment

Netherlands

Trial participating centre

Amsterdam University Medical Centers location AMC
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Sponsor information

Organisation

Amsterdam UMC Department of Hematology

Sponsor details

Meibergdreef 9
Amsterdam
1105AZ
Netherlands
+31205665785
m.j.kersten@amc.nl

Sponsor type

University/education

Website

www. amc.nl

Funders

Funder type

Not defined

Funder name

Netherlands Organisation for Scientific Research (NWO)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Landsteiner Foundation for Blood Research

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

AMC Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

A report of the first interim analysis including 7 patients is now in preparation. At the end of follow up (expected Q1 of 2019), a report including all 15 patients will be prepared. In the latter report, data on microbiome changes and immunological parameters will also be included.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr MD Hazenberg (m.d.hazenberg@amc.nl), after the follow up of the last patient has been finalized (expected early January 2019). Data on safety and preliminary results are available any time, please contact Dr Hazenberg by email. There are no ethical or legal restrictions. Informed consent was obtained from all participants.

Intention to publish date

01/08/2018

Participant level data

Available on request

Basic results (scientific)

Complete response: 5
Non-responders/stable disease : 2

Publication list

Publication citations

Additional files

Editorial Notes