To study the efficacy and safety of FMT augmented by donor selection and repetitive dual route administration.To study microbiota composition, functional and metabolic changes as a result of dietary modulation and FMT.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of study subjects in clinical and
endoscopic remission per adapted Mayo: stool frequency subscores (SFS) <= 1,
rectal bleeding subscore (RBS)=0 and endoscopic subscore <= 1
Secondary outcome
- Proportion of patients with a clinical response per Adapted Mayo at week 8:
decrease from baseline >= 2 points and >= 30% plus a decrease in RBS >= 1 or an
absolute RBS <= 1
- Proportion of patients with >=1 point reduction in summed endoscopic Mayo
score of both the rectum and sigmoid at week 8.
- Proportion of patients in sustained steroid-free remission per adapated mayo
at week 12: stool frequence subscore (SFS) <= 1, rectal bleeding subscore (RBS)
= 0 and endoscopic subscore <= 1 and no need for rescue therapy until week 8.
- Proportion of patients in clinical response per partial adapted Mayo (without
endoscopy) at week 8: decrease from Baseline >1 points and >30% plus a decrease
in RBS >1 or an absolute RBS <= 1
- Proportion of patients in clinical remission per full mayo at week 8 : Full
mayo score <= 2 with no subscore > 1
- Proportion of patients with:
o Endoscopic improvement: Endoscopic subscore of 0 or 1 at week 8
o Endoscopic remission: endoscopic subscore = 0 at week 8
o Histological Remission: Geboes score of < 2,0 at week 8, change in Robarts
histopathology index
o Change in IBDQ-control from baseline to week 2,4,8,18,39 and week 52
o Change in SSCAI from baseline to week 1,2,3,4,8,18,39 and week 52
o Change in Partial Mayo from baseline to week 1,2,3,4,8,18,39 and 52.
o Occurrence of adverse events
Background summary
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the
colon that affects approximately 40,000 individuals in The Netherlands.
Complaints such as abdominal pain, cramps and bloody diarrhoea usually start in
early adulthood and lead to life-long substantial morbidity. The cause of UC is
unknown, but the prevailing hypothesis is that there is a disproportionate
immune response to the host gut microbiota. Many observational studies have
shown a dysbiosis of the gut microbiota in UC. An attractive way to modulate
this interaction is to radically reset the microbiota by fecal microbiota
transplantation -or transfer- (FMT) from a healthy individual to a patient. We
recently completed a randomized trial comparing FMT from a healthy donor with
infusion of autologous feces in UC patients. In this phase 2a proof-of-concept
trial, there was no statistically significant difference in clinical and
endoscopic remission between patients with UC who received fecal transplants
from healthy donors (30.4%) and those who received their own fecal microbiota
(20.0%), which may be due to limited numbers. However, the microbiota of
responders had distinct features from that of nonresponders, warranting further
study. We next found that patients who received donor feces from a healthy
individual rich in certain Clostridium clusters IV and XIVa and with a low
abundance of Ruminococcus gnavus, had a high chance of sustained clinical
remission. We hypothesize that by preselecting favorable donors, augmenting
engraftment by rigorous prior bowel cleansing and dual and repetitive
administration of :25 gr of feces per donation we can boost the treatment
efficacy of FMT in UC patients.
Study objective
To study the efficacy and safety of FMT augmented by donor selection and
repetitive dual route administration.
To study microbiota composition, functional and metabolic changes as a result
of dietary modulation and FMT.
Study design
Randomized, double-blind, placebo controlled, multicenter, parallel group phase
II trial with open label extension possibility.
Intervention
One group will be treated with faecal transplantation from a healthy donor, the
other group will be treated with autologous faeces as a placebo.
Study burden and risks
FMT will be administered by nasojejunal tube at week 0 and week 3 as well as by
retention enema at week 0, 1, 2, and 3. Nasojejunal tube placement will be
performed by a Cortrak procedure. This procedure is routine in all
participating centers and is associated with a very small risk of
complications. The same holds for sigmoidoscopies, which patients will have to
undergo three times with biopsies (for the non-responder group this will be
four times).
Total follow-up time will be 52 weeks, during which 11 study visits are
planned. From our earlier trials we know that nasojejunal FMT administration is
well tolerated. In TURN1 out of 100 administrations vomiting was seen on two
occasions. Most patients complained of transient borborygmi and in two patients
transient fever was seen. No serious adverse events attributable to FMT have
been encountered in a total experience with nasojejunal FMT administration in
over 500 study subjects in the AMC. Donors and patients will be asked to fill
in an dietary questionnaire.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
• Age >=18 and <70
• Ability to give informed consent
• Established ulcerative colitis with known involvement of the left colon
according to the Lennard-Jones criteria
• Full Mayo score 5-9
• Endoscopic Mayo score of >= 2 in either the rectum or sigmoid upon screening
sigmoidoscopy
• Stable dose of thiopurines, 5-ASA, in preceding 8 weeks, stable budesonide
use in preciding 2 weeks, prednisone use <=15mg/day in preceding 2 weeks with a
mandatory taper of 5mg per week from week 4
• Women need to use reliable contraceptives during participation in the study
* Alkaline phosphatase >1.5x ULN in the subgroup of PSC/UC patients
Exclusion criteria
• Condition leading to profound immunosuppression
o For example: HIV, infectious diseases leading to immunosuppression, bone
marrow malignancies
o Use of systemic chemotherapy
o Child-Pugh B liver cirrhosis
• Anti-TNF treatment in preceding 2 months
Vedolizumab, tofacitinib and/or ustekinumab treatment in preceding 2
months
• Cyclosporine treatment in preceding 4 weeks
• Use of Methotrexate in preceding 2 months
• Prednisolone dose > 15 mg/day in preceding 2 weeks
• Use of topical therapy in preceding 2 weeks
• Life expectancy < 12 months
• Difficulty with swallowing
• Use of systemic antibiotics in preceding 4 weeks
• Use of probiotic treatment in preceding 4 weeks
• Positive stool cultures for common enteric pathogens (Salmonella, Shigella,
Yersinia, Campylobacter, enteropathogenic e coli)
• Positive C. Difficile stool test
• Positive dual faeces test for pathogenic parasites e.g. Dientamoeba
histolytica, Giardia Lamblia, Dientamoeba fragilis..
• Positive serological test for HIV
• History of surgery:
o presence of a pouch
o presence of stoma
• Known intra-abdominal fistula
• Pregnancy or women who give breastfeeding
• Vasopressive medication, icu stay
• Signs of ileus, diminished passage
• Allergy to macrogol or substituents, eg peanuts, shellfish
* Allergy to gadolinium iv contrast agent in the subgroup of patients who
will be scheduled for MRI liver.
• Crohn*s disease
* Subject who has any conditions that in the opinion of the investigator,
would compromise the safety of the subject or the quality of the data and is an
unsuitable candidate for the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL65069.018.18 |
| OMON | NL-OMON20218 |