The main objective of this study is to investigate gender differences in P-gp function at the blood brain barrier, in order to gain further insight into the impact of these differences on the action of pharmaceuticals (antidepressants and…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
transporterfunctie op de bloed-hersenbarriere
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PET images will be analysed using PMOD software (PMOD technologies, Zurich,
Switzerland, version 4.1). Predefined brain regions based on a maximum
probability map are selected as volumes of interest (VOIs). Tracer kinetics of
[18F]MC225 reflect the BBB P-gp function and will be assessed as outcome
measure for P-gp efflux function. Those will be compared in between the groups
of male and female subjects.
Secondary outcome
not applicable
Background summary
P-gp is one of the main efflux transporters at the blood-brain barrier and is
responsible for the transport of a variety of neurotoxic substances, including
pharmaceuticals. Multiple studies report gender differences in therapeutic
outcomes, toxicity and side effects for many drug agents. P-gp plays an
important role in the bio-availability, drug distribution, metabolism and
elimination of pharmaceuticals labelled as P-gp substrates (e.g. the majority
of antidepressants and antipsychotics). A difference in P-gp function was
already reported in hepatic P-gp expression. The aim of the current study is to
evaluate the influence of gender on cerebral P-gp function. Outcomes of this
study can be of great importance in gender-based prescription of P-gp substrate
pharmaceuticals.
Study objective
The main objective of this study is to investigate gender differences in P-gp
function at the blood brain barrier, in order to gain further insight into the
impact of these differences on the action of pharmaceuticals (antidepressants
and antipsychotics) in the brain.
Study design
10 healthy volunteers (5 male, 5 female subjects) will undergo a 60 minute
dynamic [18F]MC225 PET scan with arterial sampling. Design: observational
study.
Study burden and risks
[18F]MC225, a weak P-gp substrate, proved a suitable tracer for PET imaging and
quantification of the P-gp transporter in animal (rat and NHP) studies. Since
[18F]MC225 is a PET tracer, the mass of the injected drug is very low (<=100 µg)
and no pharmacological effect of [18F]MC225 is expected. In recent human
studies in healthy volunteers no side effects were reported. Study subjects
will receive a low dose of radiation during the PET scans. The total effective
dose is established by a radiation expert and is 3.3 mSv, which is below the
effective annual radiation dose limit of 20 mSv/y.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Age: 50-80 years
- MMSE: 28-30
- No history of any neuropsychiatric disorders that might affect the P-gp
function or blood-brain barrier integrity
Exclusion criteria
- Use of medication with known P-gp affinity
- History of neuropsychiatric disorders affecting the P-gp function or
blood-brain barrier integrity
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 | EUCTR2022-003664-25-NL |
| CCMO | NL83060.042.22 |