The aim of this study is to determine whether dopamine modifies the metabolic activity of BAT. Furthermore, we want to investigate the relation between the metabolic activity of BAT with energy expenditure and glucose tolerance in these individuals…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Lifestyle issues
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate whether bromocriptine influences the metabolic activity of BAT,
as assessed with a FDG-PET CT scan
Secondary outcome
1) To investigate whether peripheral factors affect the (supposed) central
effect of bromocriptine on BAT activity as assessed with FDG-PET CT scan by
combining bromocriptine with domperidone.
2) To determine whether the difference in resting energy expenditure during
thermoneutral conditions correlates with the metabolic BAT activity as assessed
with FDG in subjects using nothing compared to bromocriptine or bromocriptine
compared to bromocriptine combined with domperidone.
3) To determine if the glucose tolerance (as assessed with HOMA-indexes)
correlates with metabolic BAT activity as assessed with FDG in subjects using
nothing compared to using bromocriptine.
4) To determine if the sympathetic tonus (as assessed with continues blood
pressure measuring using the fina press) differs when using bromocriptine or
bromocriptine combined with domperidone as compared to nothing.
Background summary
Obesity and diabetes mellitus type 2 (DM2) are health problems with a
tremendous impact. Many attempts have been made to combat obesity and DM2,
however, a breakthrough therapy is still lacking.
Bromocriptine, a dopamine 2 receptor agonist, has recently been approved in the
treatment of diabetes mellitus type 2. Bromocriptine causes a significant
improvement of fasting plasma glucose and Hba1C values. Though the central
working mechanism is partially known, how bromocriptine exerts its effects
peripheral is still unknown.
Brown adipose tissue (BAT), known for its capacity to dissipate excess energy,
may be involved in this process as stimulation by the sympathetic nervous
system is the principal driving force in controlling BAT activity. Animal
studies performed so far show inconsistent results for the role of dopamine on
the sympathetic nervous system on BAT activation. Methodologically, these
studies are difficult to compare so a clear conclusion on the role of
bromocriptine on BAT activity is still lacking. Up until now, there are no
results with regard to the effect of dopamine on BAT activity in humans.
However, since the sympathetic nervous system is the principal driving force in
controlling BAT activity and the use of bromocriptine has shown to increase
resting energy expenditure (REE), we do think bromocriptine does stimulate BAT
activity. Co-administration of bromocriptine with domperidone (a peripheral
dopamine antagonist), will enable us to discern the central and peripheral
effects of bromocriptine. Subjects will be randomized to group 1 (nothing vs
bromocriptine) or group 2 (bromocriptine vs bromocriptine + domperidone).
Metabolically active BAT can be detected by PET-CT scans using
18F-fluorodeoxyglucose (18F-FDG), which is a radio labelled glucose molecule.
In this study we aim to investigate the influence of bromocriptine on BAT
activity. We will perform a FDG-PET-CT scan in group 1: before and after the
use of bromocriptine for 2 weeks and in group 2: after the use of bromocriptine
for 2 weeks and after the use of bromocriptine combined with domperidone for
two weeks.
Study objective
The aim of this study is to determine whether dopamine modifies the metabolic
activity of BAT. Furthermore, we want to investigate the relation between the
metabolic activity of BAT with energy expenditure and glucose tolerance in
these individuals.
Study design
Study design: Observational design with invasive measurements.
Included subjects will visit the AMC hospital on 3 occasions.
Visit 1: Informed consent, medical history, vital signs, laboratory
measurements, and blood pressure variability (fina press). Total blood drawn:
20ml.
Group 2: start using bromocriptine with or without domperidon for 2
weeks.
Visit 2: Core body temperature will be measured using a body core pill,
subjects will swallow them 3 days before the visit and return them on the visit
day. Resting energy expenditure after 30 minutes rest. Oral glucose tolerance
test, and intravenous administration of the radioactive farmacon FDG and
FDG-PET CT- scan. Total blood drawn: 60 ml.
Group 1: start using bromocriptine
Group 2: start using bromocriptine with or without domperidon for 2
weeks.
Visit 3(2 weeks after visit 2): same as visit 2
Study burden and risks
Included subjects will visit the AMC hospital on 3 occasions.
Visit 1: Informed consent, medical history, vital signs, laboratory
measurements, electrocardiogram (ECG) and blood pressure variability (fina
press). Total blood drawn: 20ml.
Group 1: start using bromocriptine for 2 weeks.
Visit 2:Core body temperature will be measured using a body core pill, subjects
will swallow them 3 days before the visit and return them on the visit day.
Resting energy expenditure after 30 minutes rest. Oral glucose tolerance test,
and intravenous administration of the radioactive farmacon FDG and FDG-PET CT-
scan. Total blood drawn: 60 ml.
Group 1: start using bromocriptine + domperidone
Group 2: Start using bromocriptine for 2 weeks.
Visit 3(2 weeks after visit 2): Same as visit 2
The resulting dose from the radioactive tracers + the scans is 10.0 mSv. The
placement of an intravenous canula can be an unpleasant experience and there is
a small chance of developing flebitis at the site of the intravenous canula.
The placement of the rectal thermometer can be an unpleasant experience. While
using the study medication the subjects can encounter side effects of the
medication.
There is no benefit for the volunteers. This research will provide insight into
the mechanism of brown fat activation, which may help us to develop methods to
combat obesity and diabetes.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Male Caucasian Origin 18-30 years old BMI range 19-25kg/m2 Subjects should be able and willing to give informed consent.
Exclusion criteria
Renal failure (creatinine >135 mmol/L), liverfailure (AST/ALT > 3 times higher than the normal upper value), Daily use of prescription medicine or drug use, Prior participation in a research protocol involving radiation exposure in the last 2 years, Known hypersensitivity to bromocriptine, domperidone maleate or other ergot alkaloids. Uncontrolled hypertension. Known history of coronary artery disease, or other severe cardiovascular conditions (such as a prolonged Qtc-time), or symptoms / history of severe psychiatric disorders. Known cardiac valvulopathy
Prolactin-releasing pituitary tumour (prolactinoma).Cases where stimulation of the gastric motility could be harmful: gastro-intestinal haemorrhage, mechanical obstruction or perforation.
Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
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 | NL44695.018.13 |