The aim of this study is to determine whether subcutaneous administration of insulin detemir, as compared to NPH insulin, leads to a more pronounced effect on brain glucose metabolism and blood flow in brain regions associated with appetite…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study endpoints:
I. Cerebral metabolic rate of glucose (CMRglu), in brain regions associated
with appetite regulation, as determined by FDG-PET scanning
II. Cerebral blood flow (CBF), in brain regions associated with appetite
regulation, as determined by H2O-PET scanning
Secondary outcome
Secondary study endpoints:
I. Insulin concentrations in the CSF
II. Brain activity in specific regions involved in control of appetite, as
determined by fMRI
III. Weight change
Background summary
Intensive insulin therapy improves the long-term outcome of diabetes patients,
but is also associated with weight gain, a very unwanted side-effect. Insulin
detemir is a relatively new basal insulin analogue, which consistently has been
shown to result in less weight gain as compared to NPH insulin. This
observation has so far not been explained. However, a possible mechanism could
be an enhanced effect of insulin detemir in cerebro in communicating satiety
signals. Since insulin receptors are abundantly present in the brain, it is of
interest to assess whether reduced weight gain is associated with increased
concentrations of insulin detemir in the cerebrospinal fluid (CSF) and whether
there are differences in glucose metabolism and blood flow in brain areas
potentially involved in appetite regulation.
Study objective
The aim of this study is to determine whether subcutaneous administration of
insulin detemir, as compared to NPH insulin, leads to a more pronounced effect
on brain glucose metabolism and blood flow in brain regions associated with
appetite regulation. Furthermore, we would like to explore whether insulin
detemir, as compared with NPH insulin, reaches a higher concentration in the
CSF, whether it leads to more activation in appetite related brain areas and
whether the changes in appetite control are related to changes in brain glucose
metabolism, blood flow and/or insulin concentration in the CSF, as potential
explanation for the weight difference of insulin detemir.
Study design
Randomised, open-label cross-over study. Type 1 diabetic patients will be
treated on a basal-bolus regimen for two periods of 12 weeks, starting with
either insulin detemir or NPH insulin, administered in the evening, the
prandial insulin being insulin aspart. PET and fMRI measurements and a lumbar
puncture will be performed in the last week of both treatment periods.
Intervention
12 weeks of insulin detemir QD in the evening (+ TID insulin aspart)
12 weeks of NPH insulin QD in the evening (+ TID insulin aspart)
Study burden and risks
We are well aware, that this study can be a really demanding task for our
patients. Participants will have to switch to another insulin therapy scheme
(although it is possible that they already use or have used the trial insulin
before), which can be really hard. After a screening visit they are to visit
the research facility five times. These visits will be in the early morning.
The risks associated with participation are the risks of venous/arterial blood
drawing, lumbar puncture and radioactivity (<10mSv)during PET scanning, as
described in full detail before. We will try to make this study as bearable as
possible for our patients. All posible measures will be taken to minimize the
discomfort for the participants. All tests will be done by one researcher.
From experience at our own institution, it is known that the participating
patients are very enthusiastic during the study, mostly because of their
interest in the scientific background of their disease.
De Boelelaan 1117
1081 HV Amsterdam
NL
De Boelelaan 1117
1081 HV Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Type 1 diabetic patients
Age 21-60 years
Male
Diabetes duration minimal 2 years
HbA1c ~ 7,5%
Exclusion criteria
Recent onset of DM
BMI < 18 OR > 35 kg/m2
T2DM
History of major heart/renal disease
Severe untreated proliferative retinopathy
History of recurrent severe hypoglycaemia
(History of) brain disorders
Alcohol abuse
(History of) drug abuse, benzodiazepines, selective beta-blockers, oral steoids, oral anticoagulants
Current psychiatric disease/treatment
(history of) eating disorders
History of severe head trauma accompanied by loss of consciousness
Any endocrine disease not well controlled for at least 3 months
Inability to undergo MRI
Visual acuity < 0.3
Known or suspected allergy to trial product or related products
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2007-007255-13-NL |
| ClinicalTrials.gov | NCT00626080 |
| CCMO | NL20992.029.08 |