The main objective for the current project is to investigate the effect of acute systemic inflammation - induced by LPS exposure - on energy metabolism, measured as resting metabolic rate (RMR), in apparently healthy volunteers.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Energieverbruik
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is energy metabolism in apparently healthy
volunteers.
Secondary outcome
Secondary outcome parameters are substrate oxidation, glucose and lipid
metabolism, hepatic, kidney and pancreatic function, vascular function,
oxidative stress and clinical and inflammatory parameters.
Background summary
Patients in the ICU are often critically ill and are sometimes being fed via
enteral nutrition. In addition, these patients often have a highly variable
energy expenditure which is changing in time. To maintain in energy balance, it
is important to understand the effect of inflammation on energy expenditure and
substrate utilization to better tailor the amount and composition of tube
feeding. Intravenous injection of purified lipopolysaccharide (LPS) - a
component of the outer membrane of Gram-negative bacteria - into healthy
subjects is a well-characterized model of human inflammation. In this current
study, we want to use LPS to measure how energy metabolism and substrate
utilization is affected by inflammation.
Study objective
The main objective for the current project is to investigate the effect of
acute systemic inflammation - induced by LPS exposure - on energy metabolism,
measured as resting metabolic rate (RMR), in apparently healthy volunteers.
Study design
The study is a single-blind, randomized, placebo-controlled, cross-over study
to evaluate the effects of acute LPS exposure on energy metabolism, substrate
utilization and lipid and glucose metabolism, hepatic, kidney, pancreatic and
vascular function.
Study burden and risks
During a screening visit, a physical examination takes place. Body weight and
height will be determined and heart rate and blood pressure will be measured. A
urine dip-stick pregnancy test will be used for women only to exclude
pregnancy. Thereafter a fasted blood sample will be obtained and to assess a
normal cardiac function, an electrocardiogram (ECG) will be performed.
Each participant will be studied twice and during both periods (each period has
a duration of 10 hours), subjects will stay in a monitored ward at the MUMC+.
Two intravenous catheters will be inserted and a feeding tube will be placed.
Participants will also be asked to wear a continuous glucose monitor, an
ambulatory blood pressure device, an activity tracker and wearables to assess
body temperature, respiration rate and oxygen saturation. On several
timepoints, participants will be asked to perform cognitive tests on an iPad,
while wearing glasses that record eye tracking movement. During this stay,
whole body energy expenditure and substrate metabolism will be continuously
measured in the respiration chamber. At the monitored ward in the hospital,
this will be done in regular 30-minutes interval, depending on the well-being
of the participants. Venous blood will be collected directly before LPS
injection at regular intervals thereafter. Moreover, 24h urine will be
collected in batches.
After both periods, subjects will return to the university for a follow-up
meeting where a postprandial test will be performed. Subjects are requested to
consume a standardized mixed meal and blood samples will be collected at
regular intervals. Energy expenditure and substrate metabolism will be measured
by ventilated hood measurements. Between the test day and the follow-up
meeting, 48h glucose profiles, 48h blood pressure profiles and 48h activity
monitoring will be measured.
Venepuncture and insertion of a cannula can cause discomfort and possibly a
local haematoma or bruise. Indirect calorimetry might evoke claustrophobic
reactions, but there are no physical risks involved. Total time investment will
be approximately 31 hours and 361.5 mL blood will drawn during a period of 6
weeks. Time invested is excluding travel time.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
• Provision of signed and dated informed consent prior to any study specific
procedures
• Willingness to comply with study protocol
• Apparently healthy men and women as judged by the study physician
• Non-smoking
• Aged between 18 and 35 years
• BMI >=20 and <=25 kg/m2
• Agreeing to be informed about medically relevant personal test-results by a
physician
Exclusion criteria
• Having a medical condition or use of medication which might lead to an
intensified response towards LPS exposure to be judged by the study physician
• Having a medical condition or history which might impact study measurements
to be judged by the study physician (e.g. myocardial infarction, angina,
thrombosis, stroke, cancer, liver or bowel disease or diabetes)
• Use of over-the-counter and prescribed medication, which may interfere with
study measurements (to be judged by the principal investigator and physician)
• Use of oral antibiotics (with the exception of topical antibiotics) in 40
days or less prior to the start of the study
• Current use of antihypertensive, antidiabetic or lipid lowering medication
• Females who are pregnant, breast feeding or may wish to become pregnant
during the study
• Abnormal ECG result
• Fasting glucose >7.0 mmol/L
• Total cholesterol >8.0 mmol/L
• Clinically significant out of range values of serum levels of liver, kidney
and pancreatic enzymes, to be judged by the study physician
• Anaemia, Hb-level <7.8 mmol/L (female) and <8.3 mmol/L (male)
• Body mass index < 20 kg/m2 or > 25 kg/m2
• Reported alcohol consumption > 14 units/week (female) or > 21 units/week
(male)
• History of illicit drug use
• Reported weight loss or gain of 3 kg or more during a period of 2 months
prior to screening
• Active blood donor (<3 months prior to start study)
• Use of an investigational product in another biomedical study within the
previous month
• Having a history of spontaneous vagal collapse
• Having participated in a previous trial where LPS was administered
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 | NL78277.068.21 |