The primary objective of the present study is to investigate if the intestinal permeability is increased in patients with an acute COPD exacerbation. To investigate this objective, the following research question have been formulated:- Is intestinal…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters: intestinal damage and permeability, which will be
analysed by several markers in urine and plasma.
- Multi-sugar permeability test
The sugar mixture contains lactulose, sucralose, rhamnose and erythritol.
Lactulose and rhamnose are often used as a marker for small intestinal
permeability since they are degraded by the bacterial flora in the colon.
Sucralose and erythritol can be used as a marker for whole gut permeability
since they resist colonic bacterial fermentation. In combination with the
lactulose/rhamnose data they provide an insight in colon permeability.
- Determination of intestinal cell damage
Intestinal fatty acid-binding protein (IFABP) is a small cytosolic protein
present in absorptive epithelial cells, and is expressed in all parts of the
intestine (small intestine and colon, but with the highest expression in the
jejunum). In case of intestinal cell damage, these proteins leak from the cells
into the circulation and can be measured in plasma.
- Determination of epithelial tight junction proteins in blood and urine
The loss of tight junction protein claudin 3 in the intestinal epithelium
correlates with the appearance of the proteins into plasma and urine.
Secondary outcome
In venous blood, additional markers will be analysed:
Inflammatory markers
Plasma markers of inflammation will be measured to test a correlation between
systemic inflammatory markers and markers of intestinal permeability.
Background summary
Acute respiratory failure is frequently present in patients admitted with acute
exacerbation of COPD. Hypoxemia often is present in these patients but also in
patients admitted with AECOPD. Hypoxia might have multiple detrimental effects
of which gastrointestinal permeability has gained interest recently. In
patients with chronic heart failure, also known to suffer from hypoxic
episodes, increased intestinal permeability was recently shown. Its role in
exacerbation COPD with acute respiratory failure is not investigated yet but it
is supposed to have negative effects on morbidity and clinical course. We
hypothesize that COPD leads to an increased intestinal permeability by local
oxygen deficit. It could be possible that this has a negative effect on the
clinical course of acute hospitalized COPD exacerbations with or without
respiratory failure.
Study objective
The primary objective of the present study is to investigate if the intestinal
permeability is increased in patients with an acute COPD exacerbation. To
investigate this objective, the following research question have been
formulated:
- Is intestinal permeability index increased in patients admitted for an acute
exacerbation of COPD compared with the permeability index in the same patients
in stable COPD condition?
Study design
This study will be a observational single-centre study. Until now, no studies
were done investigating the intestinal permeability in COPD patients with an
acute exacerbation, so a lot of new information about the intestinal
permeability during exacerbations can be gathered by this project. The study
will be carried out at MUMC+ and contains COPD patients admitted to the
hospital with an acute exacerbation. The study will not interrupt in the
standard care of the exacerbation.
The same study procedures will take place in the first 72 hours of the hospital
admission and (at least) 28 days after the first test day.
After overnight fast, a sugar solution will be orally ingested, after
collection of a baseline blood and urine sample. Until 1h before the intake of
the sugar solution, subjects are allowed to drink water ad libitum. Thereafter,
subjects are allowed to drink a maximum of 500ml water per hour. An hour after
intake of the sugar solution a standard breakfast will be served. All produced
urine will be collected during 5h after drinking the sugar mixture.
Intervention
Intake sugarsolution
Study burden and risks
The additional test is ingesting the sugar solution and collecting venous blood
and urine. These actions are virtually without any risks. The blood sampling
will occur through an insertion of a cannulla into the vein and a bleu spot may
occur. For the ingestion of the sugars, virtually no risks are expected. Over
consumption of artificial sweeteners can result in pompous feeling, combined
with flatulation and accelerated intestinal transit. The amount of the sugars
consumed in the present study are however low and no adverse effects are
expected.
There is no direct benefit of participating in the study. In general, receiving
more insight in the role on the intestine in the systemic manifestation of COPD
will enhance our insight in the extra-pulmonary pathology of COPD and the
clinical course of de admission in acute exacerbation COPD patients. This will
result in a better (pharmacological or nutritional) treatment of the patients.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of COPD stages I-IV as defined by the (GOLD)(7);
- At admission the diagnosis AE-COPD as defined by the (GOLD)(7);
- Both male and female, age-range from 40 years;
- Hypoxemia of PaO2 < 8.7kPa at the moment of hospital admission before administration of medicines;
- Presence of other non-gastro-intestinal related and non-renal chronic diseases are allowed in case the clinical status is stable for at least 4 weeks before the study, except cardiovascular disease;
Exclusion criteria
*Participation in any other study involving investigational or marketed products concomitantly or within two weeks prior to entry into the study;
*Any kind of acute gastro-intestinal complaints or active gastro-intestinal disease;
*The presence of decompensated hearth failure, assessed by analyses of plasma pro-BNP levels;
*Use of NSAIDin the past 48 hours before the tests (ibuprofen, naproxen, meloxicam, diclofenac) with the exception of acetylsalicic acid
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 | Na goedkeuring registratie in Nederlands trialregister |
| CCMO | NL45056.068.13 |