The primary objective of this study is to explore if faecal 5-ASA levels are correlated with flares or with response to 5-ASA therapy in patients with UC. The secondary objectives of this study are to determine if faecal N-Ac-5-ASA concentration,…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Included patients will be divided in two groups: active disease and clinical
remission. Patients will start collected urine and faeces (for 1 and 3 days,
respectively) 5 days before endoscopy. During endoscopy mucosal biopsies will
be collected. The 5-ASA and N-Ac-5-ASA concentration will be determined using
quantitative HPLC analysis.
The main study parameters/endpoints include: 5-ASA concentration in faeces,
expressed in mgs in patients with active and quiescent disease.
Secondary outcome
- faecal excretion of 5-ASA in 24-hours faeces expressed in % of ingested dose
- faecal excretion of 5-ASA in 24-hours faeces expressed correlation to dry
weight
- faecal N-Ac-5-ASA concentration in 24-hours faeces expressed in % and mg and
in relation to dry weight
- mucosal 5-ASA and N-Ac-5-ASA concentration in colonic biopsies expressed in
ng/mg
- 5-ASA and N-Ac-5-ASA concentration in 24 hours urine expressed in % and mg
- composition of gut microbiome
All in patients with active and quiescent disease ulcerative colitis
Background summary
Oral 5-aminosalicylic acid (5-ASA) is an effective and widely used treatment
for ulcerative colitis (UC). The mechanism of action is unknown, but thought to
be topical rather than systemic. The concentration of 5-ASA (and the inactive
metabolite N-Ac-5-ASA) can be measured in plasma and urine but this reflects
the systemic uptake and not the exposure of the drug to the mucosa. Limited
data suggest that the concentration of 5-ASA in the rectal or colonic mucosa is
higher in patients in clinical remission as compared to patients with active
UC. Surprisingly, almost no data on faecal excretion of 5-ASA or N-Ac-5-ASA in
UC patients and healthy volunteers are available. We propose to study faecal
excretion of 5-ASA and its putative association with remission and active UC.
Potentially, this marker could be used for therapeutic drug monitoring of 5-ASA
therapy in UC patients in the clinical setting. Through therapeutic drug
monitoring, the dose and frequency of 5-ASA will be optimized for the
individual patient. On top of that, we will determine the gut microbiome in UC
patients and their rol in drug metabolism, like 5-ASA.
Study objective
The primary objective of this study is to explore if faecal 5-ASA levels are
correlated with flares or with response to 5-ASA therapy in patients with UC.
The secondary objectives of this study are to determine if faecal N-Ac-5-ASA
concentration, mucosal 5-ASA (and N-Ac-5-ASA) concentration and urine 5-ASA
(and N-Ac-5-ASA) concentration are correlated with response to 5-ASA therapy in
patients with UC. In addition, we aim to study the inter- and intra-individual
variation of faecal 5-ASA (and N-Ac-5-ASA) levels, and the gut microbiome
(mucosa, faeces) of the UC patient
Study design
Observational cohort study.
Study burden and risks
Collection of faeces over three consecutive days and urine for 24 hours. All
patients will receive usual clinical care. Patients not using Pentasa 3 gram
per day but another 5-ASA formulation 2.0-4.8 gram per day will switch their
5-ASA formulation to Pentasa 3 gram per day for two weeks: this cause not any
risk for the patient but could be any burden for the patient. During endoscopy,
four extra biopsies will be taken. The additional risk of bleeding and
perforation, associated with taking these biopsies, is very small (1:1000) and
these complications can almost always be managed endoscopically.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
In order to participate in this study, a subject must meet all of the following criteria:
- Patients >18 year old with established ulcerative colitis in care in the UMC Utrecht
- Indication for an endoscopy (diagnostic endoscopy during a flare or regular surveillance endoscopy during clinical remission; colonoscopy or sigmoidoscopy)
- Using an oral 5-ASA formulation (except a prodrug) per day for at least two weeks in a dose of 2.0 until 3,0 gram/day during active disease (thus endoscopy for flare) or 2.0 until 4.8 gram/day during remission (endoscopy for surveillance)
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Previous intestinal surgery (with the exception of appendectomy)
- Need for surgical interventions
- Active use of laxatives (bisacodyl, poly ethyleen glycol / Pegol) or anti-diarrheal mediation (opioids, codeine, loperamide)
- Combination use with other 5-ASA formulations (enema, suppository)
- Pregnancy
- Stool frequency less than 1 time a day (slow intestinal transit time)
- Uncontrolled or sever liver, renal, cardiac or pulmonary disease:
o Liver: Child-Pugh score > 7
o Renal: GFR < 60 ml/min for more than 3 months
o Pulmonal: COPD GOLD stage 3-4, need of oxygen supply at home, or uncontrolled asthma
o Cardiac: heart failure NYHA class 3-4 or myocardial infarct in the past 12 months
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 | NL62046.041.17 |