The primary objective of this study is to validate 31P-MRS as a non-invasive in vivo measure of mitochondrial function. Secondary objectives are to determine whether there is mitochondrial dysfunction in the heart of type 2 diabetic patients and to…
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary goal is to compare in vivo with ex vivo measurements of
mitochondrial function through regression analysis.
Secondary outcome
Furthermore markers of PPAR-expression will be examined and statistical
analysis will be done to assess differences between groups
(diabetic/lean/obese) where P<0.05 will be considered statistically significant
different. Also liver fat accumulation will be determined with MRI in order to
asses the relationships between liver fat accumulation and cardiac metabolism.
Background summary
It has been suggested that mitochondrial dysfunction, through down-regulation
of nuclear ligands (PPARs), might play a role in the development of diabetic
cardiomyopathy. Also, mitochondrial dysfunction has been associated with other
cardiac diseases like for example chronic heart failure. However, human data on
this topic is scarce. This is due to the fact that there is no validated
measurement for assessing cardiac mitochondrial function non-invasively in
vivo. It has been suggested that measuring PCr/ATP ratio*s with 31P-MRS in the
heart, might reflect cardiac mitochondrial function. However, so far no direct
validation of this method has been performed.
Study objective
The primary objective of this study is to validate 31P-MRS as a non-invasive in
vivo measure of mitochondrial function. Secondary objectives are to determine
whether there is mitochondrial dysfunction in the heart of type 2 diabetic
patients and to determine the role of cardiac PPAR-expression in the
development of cardiac dysfunction in type 2 diabetes.
Study design
Here it concerns an observational study, where in vivo and ex vivo measurements
of mitochondrial function in type 2 diabetic, normo-glycemic obese and lean
participants are compared.
Study burden and risks
Patients will visit the University once. Total participation time in the study
will be about 5 hours. At this visit characterisation of the subject will take
place; body composition will be measured with a Bodpod measurement and basal
energy expenditure will be measured with indirect calometry. During this
measurement blood samples (4x10ml) will be drawn. Thereafter a MRS measurement
of the heart will be performed. Patients will have to lie still during 60
minutes in an MRI-scanner. Hereafter they will go to a different MRI scanner
for additional functional measurements of the heart (cardiac function
measurements and T1 mapping, this also takes about 60 minutes, contrast agents
will be used during these measurements) and liver fat accumulation will be
determined. These measurements will be performed 1 week before surgery.
Patients will undergo their regularly planned surgery, without modification.
The only addition to the procedure is the sampling of a small amount of atrial
appendage tissue. As the atrial appendage will be used to obtain access to the
heart for the heart-lung machine for extra-corporal ventilation during surgery,
the atrial appendage will be handled any way. The removal of a small amount of
tissue of the atrial appendage is quite harmless, seen that it will be opened
and incised during this procedure anyway. The cardiothoracic surgeons in the
university hospital Maastricht are experienced with this technique and are
skilled to perform this small additional procedure. Additional risks of this
study include the risk of causing bruises during the blood sampling. MRI is a
modern diagnostic tool, which does not imply significant risks (no ionizing
radiation). The use of contrast agents in the MRI is contra-indicated in
patients with poor renal function. In rare cases, contrast agents can cause
allergic reactions, therefore a medical specialist (radiologist) will always be
present during the procedure. Furthermore the measurement and contrast
injection will be given by experienced trained personnel. There are no direct
benefits for subjects participating in the study.
Universiteitssingel 50
Maastricht 6221XS
NL
Universiteitssingel 50
Maastricht 6221XS
NL
Listed location countries
Age
Inclusion criteria
- Patients undergoing elective valve replacement or cardiopulmonal bypass surgery
- Gender: male or male
- The patients should be aged 40-75 years
- The type 2 diabetic patients should be obese (BMI > 27 kg/m2) and non-insulin dependent
- The obese controls should be BMI matched with the diabetic patients (BMI > 27 kg/m2)
- The lean subjects should have a normal BMI (20-25 kg/m2)
Exclusion criteria
- Insulin dependent diabetic subjects.
- Patients with instable angina or heamodynamically instable patients
- Use of Thiazolidines (glitazone/rosiglitazone/pioglitazone/troglitazone)
- Weight gain/loss > 3 kg in the last 6 months or signs of cachexia
- Contraindications for MRI scans.
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 |
|---|---|
| ClinicalTrials.gov | NCT03049228 |
| CCMO | NL48376.068.14 |