Primary objective: to study the effect of faecal transplantation in a phase II randomised placebo controlled design on simple clinical colitis activity index (SCCAI) and endoscopic Mayo score. Secondary objective: to study intra individual changes…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Complete clinical remission (SCCAI <2).
* Reduction of Mayo endoscopic inflammation score (decrement >1)
Secondary outcome
* Adverse events (AE) at t=3, t=6 and t=12 weeks
* SCCAI score reduction at t=6 weeks (pairwise SSCAI reduction of > 1.5 points
will be regarded as a relevant reduction (10))
* Frequency of bowel movements (starting to report at t= -2 weeks)
* Reduction of Mayo endoscopic score at t=6 wk
* Time to recurrence (recurrence is defined as a SCCAI of *4 and Mayo score *1
(10))
* Intra individual changes in presence of microbial DNA in faecal samples at
t=0, t=6, and t=12 weeks after faecal transplantation.
* Intra individual changes in presence of microbial DNA in mucosal biopsies at
t=0, t=6, and t=12 weeks after faecal transplantation.
Background summary
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the
colon. Complaints such as abdominal pain, cramps and bloody diarrhoea usually
start in early adulthood and lead to life-long substantial morbidity. Despite
decades of research the etiology and pathogenesis of this disease are still
poorly understood. Hence, there is no medical treatment available that meets
the desired criteria of high efficacy versus low adverse effects. The current
prevailing hypothesis regarding the cause of UC states that the pathogenesis
involves an inappropriate and ongoing activation of the mucosal immune system
driven by the intestinal microbiota in a genetically predisposed individual.
Four non-mutually exclusive hypotheses have been proposed regarding the role of
the microbiota in IBD: (i) a dysbalance between protective and harmful bacteria
(dysbiosis hypothesis); (ii) impaired intestinal barrier hypothesis; (iii)
excessive immune response against normal microbiota; (iv) unidentified
persistent pathogen hypothesis.
There are several clinical observations that support the dysbiosis hypothesis.
(i) germ-free mice will not develop experimentally induced colitis; (ii) there
are several papers on the beneficial effects of probiotics in mild to moderate
colitis (iii) there are several case reports of patients achieving remission
after faecal transplantation. However, systematic investigation into the effect
of correcting the dysbiosis in UC has never been performed. The most radical
way to restore the presumably disturbed natural homeostasis in UC is to perform
faecal transplantation from a healthy donor.
By designing a specific treatment protocol using faecal transplantation a
unique opportunity is created to investigate the potential beneficial effects
of restoring microbial homeostasis
Study objective
Primary objective: to study the effect of faecal transplantation in a phase II
randomised placebo controlled design on simple clinical colitis activity index
(SCCAI) and endoscopic Mayo score. Secondary objective: to study intra
individual changes in microbiota composition of faeces and mucosal biopsies at
t=0, t=6, and t=12 weeks after faecal transplantation.
Study design
This is a double-blind randomized placebo controlled clinical proof-of-concept
study as well as a reversed translational part.
Intervention
Patients will be treated with faecal transplantation, processed for
duodenal-tube infusion. Faeces will be collected from a donor as well as the
patient him/herself, in which their own faeces will be used as a placebo
Study burden and risks
It seems plausible that patients have benefit from donor faeces of strictly
selected healthy donors. Sigmoidoscopies have a very small risk of
complications; the same holds for cortrak duodenal tube positioning. According
to our experience with human faecal transplantation in therapy resistant
Clostridium difficile associated colitis as well as from the pilot trial
studying the effects of faecal transplantation on obesity no serious side
effects were observed.
Postbus 22600
1100 DD Amsterdam
NL
Postbus 22600
1100 DD Amsterdam
NL
Listed location countries
Age
Inclusion criteria
*Age *18
*Ability to give informed consent
*Established left sided ulcerative colitis according to the Lennard-Jones criteria
*SCCAI (Simple Clinical Colitis Activity Index) of 4 - 11
*Endoscopic Mayo score of >1
*Stable dose of thiopurines, 5-ASA, or corticosteroids in preceding 8 weeks
*Women need to use reliable contraceptives during participation in the study
Exclusion criteria
* condition leading to profound immunosuppression
o For example: HIV, infectious diseases leading to imunosuppression, bone marrow malignancies
o Use of systemic chemotherapy
* Anti-TNF treatment in preceding 2 months
* Ciclosporine treatment in preceding 4 weeks
* Prednisolone dose * 10 mg
* Life expectancy < 12 months
* Use of antibiotics in preceding 6 weeks
* Use of probiotic treatment in preceding 6 weeks
* Positive stool cultures for common enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic e coli)
* History of surgery:
o hemicolectomie (defined as: surgery resulting in a resection of > * of the colon)
o presence of a pouch due to surgery
o Presence of stoma
* Known intra-abdominal fistula
* Pregnancy or women who give brestfeeding
* Vasopressive medication, icu stay
* Signs of ileus, diminished passage
* Allergy to macrogol or substituents, eg peanuts, shellfish
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35247.018.11 |