Gender differences in P-gp transporter function measured with [18F]MC225 PET imaging

The impact of gender differences in P-glycoprotein function measured with [18F]MC225 and PET - [18F]MC225 for measuring gender differences

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-003664-25-NL

Enrollment

Registered

2023-04-28

Start date

2023-12-21

Completion date

Unknown

Last updated

2024-01-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gender, healthy volunteers

Interventions

Product Name: [18F]MC225 Pharmaceutical Form: Injection/infusion INN or Proposed INN: [18F]MC225 Current Sponsor code: [18F]MC225 Other descriptive name: [18F]MC225 Concentration unit: MBq megabecquer

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Healthy volunteers - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5

Exclusion criteria

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 outcomes

Primary

Measure	Time frame
Main Objective: 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). Main 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. ;Secondary Objective: 1. [15O]H2O-PET influx curves will be added as variable in the kinetic analysis using PMOD, to assess possible influence of cerebral blood flow. The CBF measures obtained with [15O]H2O-PET will be compared with K1 measures of the [18F]MC225 PET scan to see if uptake of [18F]MC225 is influenced by cerebral perfusion rate. 2. Since [15O]H2O-PET is the gold standard for quantitative imaging of cerebral perfusion, the results of [15O]H2O-PET will also be compared with MRI perfusion sequences (DSC, DCE, ASL). In this way the perfusion MRI can be validated as less invasive method to measure cerebral perfusion and be used in future projects.;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: 12 months after the last PET scan	—

Measure

Time frame

Main Objective: 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). Main 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. ;Secondary Objective: 1. [15O]H2O-PET influx curves will be added as variable in the kinetic analysis using PMOD, to assess possible influence of cerebral blood flow. The CBF measures obtained with [15O]H2O-PET will be compared with K1 measures of the [18F]MC225 PET scan to see if uptake of [18F]MC225 is influenced by cerebral perfusion rate. 2. Since [15O]H2O-PET is the gold standard for quantitative imaging of cerebral perfusion, the results of [15O]H2O-PET will also be compared with MRI perfusion sequences (DSC, DCE, ASL). In this way the perfusion MRI can be validated as less invasive method to measure cerebral perfusion and be used in future projects.;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: 12 months after the last PET scan

—

Secondary

Measure	Time frame
Secondary end point(s): MRI perfusion (DSC, DCE) parameters to compare with results of the [15O]H2O-PET to enable correction for perfusion effects interfering with outcome parameters of [18F]MC225.;Timepoint(s) of evaluation of this end point: 12 months after the last PET-scan.	—

Countries

Netherlands

Contacts

Public ContactP. Mossel

University Medical Center Groningen

p.mossel@umcg.nl

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026