The aim of the studie is to determine the correlation between fat mass end the IFX concentration. Primary research question:What is the effect of fat mass percentage, measured by a validated scale, and secundaire skinfold measurement, waist…
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Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the correlation between fat mass, measured by an
validated scale, and the IFX level. This will be measured prior to the IFX
infusion. The IFX concentration will be measured and analysed in blood. Prior
to de IFX infusion the trough level will be measured (according to regular
health care). 30 minutes after the end of the infusion the top level will be
measured
Secondary outcome
Secondarily, the body composition; measured by skinfold thickness, waist
circumference, hand grip strength, BMI and body composition will be correlated
to the IFX concentration.
Furthermore, de disease activity, inflammation parameters and the amount of
adverse effects will be measured en corelated to the fat mass.
Background summary
Patients with inflammatory bowel disease (IBD), with ulcerative colitis and
Crohn*s disease as most important types, suffer from chronic recurrent
inflammatory processes in the intestine. The treatment of IBD consist, in
10-30% of the population, of anti-TNFalfa (TNFi), such as infliximab (IFX).
TNFi belongs to the biologicals, a relative new group of medication. They are
effective in the treatment of IBD, but there are also some side effects known.
The primary therapy failure rate is approximately 10-40% and the secondary
annual loss of response (LOR) is approximately 10% (1). Besides, biologicals
have high investment costs. In the current clinical practise the dose of most
of the TNFi medications are based on bodyweight, in particular infliximab.
In the study of Dotan Et al (2) the researchers investigated the effect of
several patient characteristics on the pharmacokinetic characteristics of IFX
in the treatment of IBD. They showed that there was no linear relation between
body weight and the clearance of IFX. Patients with a lower bodyweight, had a
35% lower IFX level in the serum at all tie with a fixed dosage of 5mg/kg in
comparison with patients with a weight twice as high. Due to research in the
field of the pharmacokinetics and dynamics in the past, nowadays the dosage of
IFX is based on mg/kg bodyweight. The writers of the study of Dotan et al. (2)
seems to conclude that the dosage of IFX is not optimal, and can therefore
possibly be optimized. It seems that an individual patient with a higher body
weight does not need the same amount mg/kf medication in comparison with an
individual with a lower bodyweight in order to get the same level of IFX in the
blood. Other studies also describe the fact that body composition might be a
better tool to determine the dose of IFX medication. (3,4) Body Mass Index
(BMI) is often used to describe body composition. However, BMI does not seems
to be the an ideal method for IFX dose optimization. (3,4) Nutritional status,
measured by measuring the body composition in fat mass and fat free mass, might
be a better biomarker in order to optimize the dose of IFX in comparison with
weight or possibly with BMI (2-4). Body surface, calculated from bodyweight and
height, might also be a tool in order to optimize the dosage, and is currently
used in the oncology field for the determination of pharmaceuticals.
The study of Scaldaferri et al (5), describe that patients with a high BMI, has
a higher serum level IFX 30 minutes after infusion (toplevel), in comparison
with patients with a low BMI. This difference was not seen previous to the IFX
infusion (trough level). This higher top level in patients with a higher BMI
does not seems to lead to a better response to the medication. When taking body
fat into account, there was no significant difference between top level in
patients with a high or low bodyfat percentage. From this can be hypothesized
that body composition may be a better method in order to determine the dose of
IFX.
In patients with IBD, the nutritional status is often suboptimal. The aetiology
is multifactorial, and malnutrition and malabsorption of nutrients play a role.
(6). The literature also describe a reduced muscle mass (cachexia) in these
patients (3,7). Body composition is underexposed in patients with IBD.
Given that it is described in the literature that determining the dosage of IFX
based on body weight does not seems ideal, other methods must be investigated
in order to determine a more optimal dosage. An advantage of body bodyweight is
that it is easily applicable in daily clinical practise. Therefore, it is
important that possible new methods, such as body composition, is also easily
applicable in daily clinical practise. A more optimal dose might also lead to
less side effects and a lower LOR rate. Besides, a more optimal dose might also
lead to a lower dose for some IBD patients, reducing the costs and is thereby
also interesting for financial aspects.
Therefore, the aim of this study is to investigate the effect of body
composition, body surface and BMI on the IFX serum level compared to just
determining the body weight. Besides, there will be investigated if body
composition and BMI, and their possible pharmacokinetic consequences influence
the effectiveness of the IFX medication in the IBD population.
Study objective
The aim of the studie is to determine the correlation between fat mass end the
IFX concentration.
Primary research question:
What is the effect of fat mass percentage, measured by a validated scale, and
secundaire skinfold measurement, waist cirucmference, hand grip strength, BMI
and body surface on the IFX level, with IFX dose based on the body weight, in
an IBD population using IFX medication?
Secondary research question(s)
The secondary research is question is; Is the effectiveness of IFX and the
safety (advere effects) related to the body composition in IBD patients
starting with IFX medication?
Study design
In this observational study, patients treated with IFX or patients that will
start with IFX for the treatment of IBD will be included in de study. A
transversal study design will be used in order to investigate the relation
between body composition and the IFX concentration. This will be measured in
patients already treated with IFX. Besides, patients starting with IFX during
the study period will be included. In this patients, a steady state need to be
reached in order to measure a reliable measure. Therefore the IFX concentration
will be measured after the third IFX infusion in these patients. In this
population we will also measure the effect of the IFX in a prospective setting.
All patients will be recruited from the IBD population from Zuyderland Medical
Centre location Sittard and Heerlen.
Study burden and risks
The measurements to determine the body composition, are not-invasive methods.
There are no risk or negative effects expected. Blood collection can hurt or
cause haemorrhage. The blood collection is taken from an already placed
infusion. All together, we collect 1 tube of 6 ml blood extra, above regular
care. This amount does not cause problems for adults. All other measurements
(IFX trough level, inflammation parameters in blood and calprotectine) and the
medication gifts will be done according to regular care. Therefore, there are
no extra risk here. Patients do not have to visit the hospital more often than
normal. The extra measurements fort the study will take approximately 2 hours
above regular care. The study load and risks for the participants is therefore
low.
Dr. H. van der Hoffplein 1
Geleen 6162BG
NL
Dr. H. van der Hoffplein 1
Geleen 6162BG
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
Patiënt are eligible to participate in the study if all of the following criteria are met:
1. Patient, male or female, is aged above 18 years
2. Patient has an established diagnosis of ulcerative colitis or Crohn*s disease
3. Patients is being treated with, or start with the treatment IFX for a period of at least 12 weeks, or for the first time during the study period.
4. Patiënt must be able to understand the patient information and the explanation of the investigator
5. Patient must be able to undergo the study measurements and understand the instructions of the investigator
6. Patient is informed about the intention and nature of the study including the possible risks and has signed the informed consent before inclusion.
Exclusion criteria
Exclusion criteria
Patients are not eligible if one or more of the following criteria are met:
1. Patient is mentally or physically not able to participate to the study, including severe mental illness.
2. Patient has had a change in the dosage of the IFX during the last 5 weeks.
3. Patients who is currently pregnant, breastfeeding, or is planning to become pregnant during the study period.
4. Patients suffering from severe comorbidities which can influence the body composition of the pharmacokinetics of IFX;
a. Current malignancy or a malignancy in the recent history (<5 years), except cutaneous basal cell carcinoma and cutaneous squamous cell carcinoma.
b. (history of) Liver/renal failure
c. Short Bowel Syndrome
d. Heart failure defined as; New York Heart Association (NYHA) Class III or IV
5. Patients participating in other studies, or participated I another study with an intervention in de last 4 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
In other registers
| Register | ID |
|---|---|
| CCMO | NL66944.096.18 |
| OMON | NL-OMON28109 |