The development of targeted drugs has led to an improvement in disease control, but the long-term outcomes of the disease for the individual patient are still not optimal due to the fact that these therapies do not work at all in some patients or…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Remission defined as a total Mayo score of 2 or less with a Mayo endoscopy
score of 0 or 1 (without friability) and a bleeding score of 0 at week 14.
• Clinical response at week 14 defined as total Mayo score of 2 or less with
Mayo endoscopy score of 0 or 1 (without brittleness) and bleeding score of 0
The clinical response is divided into four subcategories:
• "Superresponder":
Meets clinical response criteria at week 14
• Responder:
Mayo score: 50% reduction / >= 3 improvement from baseline, but does not meet
the criteria for remission;
endoscopic Mayo: Does not meet the criteria for clinical response, but shows a
reduction in Mayo ES
• Partial Responder:
Mayo score: reduction to 30%, endoscopic Mayo: no formal improvement from
Mayo ES but slight improvement in general physician assessment.
• Non Responder:
Reduction of less than 30% and no improvement in overall assessment at
endoscopy
Secondary outcome
• diepe klinische remissie (Mayo-score 0-1 met SF <=1 en RB = 0)
• mucosale genezing (Mayo ES = 0; Nancy histologie-index: ulceratie: 0,
neutrofielen: 0, chronisch infiltraat: 0 of 1).
• symptomatische remissie beoordeeld aan de hand van door de patiënt
gerapporteerde uitkomst PRO 2 (SF 0-1 en RB 0)
• ziekteprogressie (flares)
• complicaties tot week 52:
o ziekenhuisopnames vanwege UC
o intensivering van de behandeling inclusief introductie van toxische
langdurige therapieën (d.w.z. systemische glucocorticoïden)
o nieuwe stenose
o nieuwe fistel
o nieuwe ontwikkeling van PSC
o infecties
o darmchirurgie
Patiënten worden geclassificeerd in primaire en secundaire goed, laag en
niet-reagerend (met meting van antilichaam titers tegen geneesmiddelen en
geneesmiddelniveaus, indien beschikbaar); registratie met behulp van deze
definities en de duur van de respons volgt (om langdurige - super responser's
te identificeren als een relevante subgroep).
Background summary
There are so-called targeted therapies for the treatment of ulcerative colitis
(UC). These are biologicals, or biological medicines with small molecules in
their base. Biological medicines are antibodies directed against inflammatory
substances or cells. The small molecules work on the inside of the cells in the
body and ensure that the signal in the cell is not passed on to the cell
nucleus, thus reducing inflammation in the intestine.
The research includes a collection of biomaterials. On the basis of the
biomaterial, the course of ulcerative colitis under treatment with a biological
medicine is followed for a maximum of 2 years. The study therefore has no
influence on the normal standard disease treatment.
The study collects medical data and periodically biomaterials (tissue, blood
and feces) for analysis at the molecular level. These medical data and
biomaterials are collected simultaneously from several participating hospitals
and subsequently analysed jointly. Subsequently, there is an in-depth study to
better understand the disease mechanisms and the changes during therapy at the
cellular level, in order to allow more targeted therapy choices and adaptation
for the individual patient.
This research is carried out in the Netherlands by the Amsterdam University
Medical Center (Amsterdam UMC), location AMC in Amsterdam as a participating
center. The study is being conducted in collaboration with the University
Hospital in Leuven, Belgium, the Regional University Hospital in Nancy, France
and is led by the University Medical Center Schleswig-Holstein (UKSH), on the
campus in Kiel, Germany.
Study objective
The development of targeted drugs has led to an improvement in disease control,
but the long-term outcomes of the disease for the individual patient are still
not optimal due to the fact that these therapies do not work at all in some
patients or that the effect over time. time is wasted. At present, the expected
response to a particular drug and the further course of the disease are
unfortunately hardly predictable for the individual patient. The aim of this
research is to better understand disease mechanisms and changes during therapy
at the molecular level, in order to allow more targeted therapy choices and
adaptation for the individual patient. For this, new so-called biomarkers must
be found. In the future, the response to a biological medicine can be better
predicted at an early stage. In this way, the most suitable medicine for the
individual can be selected before the start of the therapy and we can recognize
a serious course and / or complication at an early stage of the disease.
Study design
The therapy with one or more of the biologicals concerns the groups: anti-TNF,
anti-IL12 / 23, anti-integrin and JAK inhibitors (e.g. Adalimumab, infliximab,
ustekinumab, vedolizumab and tofacitinib). The times at which outcomes are
measured and biomaterial is collected are based on the times of routine checks
during therapy with the biological drug.
Follow-up starts before the start of the first treatment with the drug (week 0
or screening), and then takes place during planned follow-up checks (at weeks
2, 6, 14, 26, 52, 78 and week 104). The time points may vary slightly depending
on your individual treatment plan determined by the treating physician. Should
one or more therapy changes be required during your treatment, the observation
plan for this new targeted drug will start over from the beginning (again from
weeks 0, 2, 6, etc. until the maximum study duration of 104 weeks is reached).
This variable observation plan enables the course of ulcerative colitis to be
viewed with different treatment schedules of targeted drugs. The observation
period of disease treatment activity is at least 1 to 2 years.
The collection of the biomaterial (tissue, blood and faeces) takes place during
the above time points. The biopsies are taken during the endoscopy at week 0
and week 14. During each hospital visit, or (follow-up) check-up, blood is
taken for analyzes (including metabolome testing, DNA testing and
pharmacokinetics).
While previous studies looked at single molecular data types (-Omics layers)
and samples (e.g. biopsies or blood), this project specifically aims to compare
local and circulating individual features or signatures of the same individual
over time and to obtain the complete range of disease activity. It is
hypothesized that this orthogonal approach increases the ability to detect
meaningful mechanisms and filter out predictive marker sets. The result of the
integrated analysis will be the guiding principle for new molecular tests for
patient stratification and treatment monitoring, that is, choosing the right
therapeutic escalation at the right time.
Study burden and risks
In this study, targeted therapies are administered to patients with ulcerative
colitis as part of standard care.
An important inclusion criterion is the prescription of targeted therapy. The
choice of medications (all of which are approved for first-line use) is by the
treating physician. All procedures are in accordance with standards of care.
Patients participating in this study can benefit from close clinical follow-up
according to clinical guidelines. A direct benefit to the individual patient
participating in this study is not expected. Results of this study may lead to
a benefit for the group of patients suffering from the same disease.
Baseline and follow-up visits include clinical evaluation, assessment of
disease activity and patient reported outcome, as well as biopsy procedures,
blood and stool samples. Blood samples will usually be taken at time points
when indicated in the clinical routine. The extra amount of blood taken during
this trial is a maximum of 45 ml per visit. Therefore, patients with baseline
hemoglobin <10 g / dl will not be enrolled.
There is no research-specific endoscopic procedure. All mucosal biopsies are
taken at clinically indicated endoscopies. Any biopsy is associated with the
risk of bleeding from where the sample was taken or a tear in the colon or
rectal wall (perforation). Additional biopsies for research purposes may
therefore theoretically lead to a slightly increased risk and an extension of
the endoscopic procedure (approximately 5 minutes).
Avenue de la Toison d'Or 56
Brussel 1060
BE
Avenue de la Toison d'Or 56
Brussel 1060
BE
Listed location countries
Age
Inclusion criteria
Prescription of a targeted therapy, choice is by treating physician:
- Anti-TNF and, or Anti-IL 12/23 and, or Anti-integrin and, or JAK-inhibitors.
1. Male and female patients >= 18 years of age (at the time of signing the
Informed Consent)
2. Signed written Informed Consent
3. Established diagnosis of ulcerative colitis with a minimum disease duration
of 3 months
4. Moderate to severe active UC, defined by Mayo Score >= 6 including endoscopy
score of >= 2
5. Indication to start any biological or small molecule agent (anti-TNF, anti-
IL12/23, anti-integrin and JAK-inhibitors)
6. In case of treatment with corticosteroid: stabile dose for at least 3 weeks
prior to baseline, dosage <= 20 mg prednisone
7. Indication for colonoscopy for the assessment of disease activity as for
standards of care and current guidelines
8. Able to comply with the study procedures
Exclusion criteria
1. Diagnosis of indeterminate colitis, microscopic colitis, ischaemic colitis,
infectious colitis, radiation colitis
2. Absolute contraindications to colonoscopy procedures, complication during
previous endoscopy
3. Bleeding disorders
4. Indication for surgery for UC
5. Legal incapacity
6. Rectal topical therapy (enemas or suppositories) <= 2 weeks prior to baseline
7. Treatment with > 20 mg prednisone within 3 weeks prior to baseline
8. anaemia (haemoglobin < 10 g/dl) at baseline
9. Pregnant or breastfeeding women
10. Any circumstances which could contradict a study participation and lead the
Investigator to assess the patient as unsuitable for study participation for
any other reason
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 |
|---|---|
| Other | 00023031 |
| CCMO | NL76502.018.21 |