The aim of this study is to explore intra-individual differences in expression of Rac1 and pSTAT3 in leucocytes of IBD patients before and during thiopurine treatment.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is intra-individual differences in Rac1 and pSTAT3
expression before and during 4 weeks of thiopurine treatment.
Secondary outcome
The secundary endpoints are:
- Assessment of number of patients with intra-individual reduction of at least
30% of Rac1 corrected pSTAT3 expression in peripheral T cells of thiopurine
derivative initiating adult IBD patients at week 4
- Assessment of number of patients with intra-individual reduction of at least
50% of Rac1 corrected pSTAT3 expression in peripheral T cells of thiopurine
derivative initiating adult IBD patients at week 4
- To measure early inhibition (at week 1) of the Rac1-pSTAT3 pathway after
starting thiopurine therapy in percentual reduction and in number of patients
with at least 30% of Rac1 corrected pSTAT3 expression in peripheral T cells
- To evaluate the correlation between 6-TGN concentrations and Rac1-corrected
pSTAT3 expression at week 1, and at week 4
Background summary
Despite several new biological treatment options for inflammatory bowel
diseases (IBD), thiopurine derivatives, such as
azathioprine (AZA) and mercaptopurine (MP), remain the gold standard of
treatment. Unfortunately, there is a delayed onset of
therapeutic response, as clinical response generally occurs after 3-4 months
after initiation of thiopurine therapy. In addition, up to
50% of patients discontinue thiopurine therapy within 2 years due to
intolerable adverse reactions or therapeutic resistance mostly
during the first months of treatment. Optimization of therapy in the early
stage is therefore warranted in order to prevent
unnecessary failure due to toxicity and/or thiopurine drug resistance.
Today, optimization of thiopurine therapy is widely performed in two ways: the
first is through blood level determinations of the drug. Secondly, genotyping
is used, where based on the DNA profile it is checked whether there is a higher
risk of getting side effects. Both strategies are recommended in the national
guideline and partly help to predict the risk of side effects. However, the
effectiveness cannot be predicted with this.
A new so-called 'pharmacodynamic marker', such as the protein called Rac1,
could be a predictor of the effectiveness of thiopurines in the future. It has
been described in the literature that the Rac1 protein is directly related to
the mechanism of action of thiopurines. In a previous study (Deben et al,
cytometry 2021) we showed that we can measure this marker in the blood.
Subsequently, a PILOT study was performed to investigate whether this marker is
useful in IBD patients, by looking at the difference of this marker between IBD
patients taking thiopurines and IBD patients taking other drugs. Clear
differences were demonstrated (unpublished data), which gave rise to new
research questions. In the PILOT study we have already shown that the amount of
Rac1 protein changes in patients taking thiopurines. We hypothesize that the
amount of Rac1 protein will also change within the same patient when he/she
starts thiopurine therapy. We expect that this difference can later be used as
an effect measure for the effectiveness of thiopurine therapy.
However, before a large observational study can be set up to compare the amount
of Rac1 with the effectiveness, we would like to investigate whether
intra-individual differences are indeed visible in the amount of Rac1 before
and during the use of thiopurine therapy. Therefore, we have now set up this
longitudinal PILOT study to test our hypothesis that there are also
intra-individual differences in Rac1.
Study objective
The aim of this study is to explore intra-individual differences in expression
of Rac1 and pSTAT3 in leucocytes of IBD patients before and during thiopurine
treatment.
Study design
a prospective observational longitudinal PILOT study
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: There is no compensation
for the participation in the study. The burden on the subjects is considered to
be minimal. Patients are treated in accordance with
the applicable national guidelines. The only burden is that 1 - 2 extra
tube(s) of 5 ml of EDTA blood will be drawn during the already
planned venipuncture to determine additional study parameters. This is the only
additional burden on the patient. The patients are
not exposed to additional risks. Feedback and recording of adverse reactions
are standard in this patient group, so that no
additional effort is required from the patient.
Dr. H. Van der Hoffplein 1
Sittard-Geleen 6162BG
NL
Dr. H. Van der Hoffplein 1
Sittard-Geleen 6162BG
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of Inflammatory Bowel Disease (IBD) (either Crohn's disease or
Ulcerative Colitis)
- Mild or Moderate-to-severe IBD patients who are starting thiopurine
treatment
- age between 18 - 70 years old
- both hospitalized and ambulant patients are eligible
Exclusion criteria
- other auto-immune diseases
- previous use of thiopurines within two weeks before inclusion
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 | NL80556.096.22 |