The primary objectives of this study are to assess the safety and estimate the radiation dose of the radioligand [18F]FB610, and to assess the optimal kinetic model for quantification of the tracer uptake. Secondary objectives are to determine…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the [18F]FB610 binding as a measure of c-Abl in
PD patients and healthy volunteers, to assess the radiation dose and assess its
safety, and to identify the most suitable tracer kinetic method for
quantification of [18F]FB610 binding.
Secondary outcome
Secondary study parameters include the difference between binding of the
radioligand [18F]FB610 in PD patients and healthy volunteers to determine
whether c-Abl expression may be increased in PD patients.
Background summary
Parkinson's disease is the second most common neurodegenerative disease. With
the new radiotracer [18F]FB610, the levels of the non-receptor tyrosine kinsae
enzym c-Abl can be measured. c-Abl activation plays a role in alfa-synuclein
accumulation and parkin inactivation, which lead to accumulation of
pathological substrates of parkin. These processess lead to neurodegeneration
in Parkinson*s disease. In this study we investigate the safety and dosage of
this new radiotracer. Additionally, we aim to investigate whether this tracer
can differentiate individuals with Parkinson's disease from healthy control
subjects. In the future, this tracer could help identify patients who are
eligbile for medical trials with c-Abl inhibitors.
Study objective
The primary objectives of this study are to assess the safety and estimate the
radiation dose of the radioligand [18F]FB610, and to assess the optimal kinetic
model for quantification of the tracer uptake. Secondary objectives are to
determine whether binding of radioligand [18F]FB610 can differentiate PD
patients and healthy volunteers and to assess the potential of [18F]FB610 for
patient selection for medical trials with c-Abl inhibitors.
Study design
This is an observational cross-sectional study. All subjects will undergo a 90
minute [18F]FB610 PET scan after injection of [18F]FB610 with continuous
arterial blood sampling, which is necessary for kinetic modelling. The dose of
[18F]FB610 will be 185 MBq.
Study burden and risks
In total there will be three visits at Amsterdam UMC: a first (screening)
visit, an MRI scan and a PET scan. Some participants with PD will need an extra
visit for a DAT-SPECT. During the screening study visit, the medical history
will be recorded, a neurological examination will be performed, questionnaires
and cognitive tests will be administered, and blood samples will be taken.
There are no risks associated with MRI acquisition after MRI safety screening.
The risks associated with PET scanning are limited, but the subjects will have
radiation burden, which will be no more than 10 mSv. During the PET scan
arterial blood samples will be taken, with a total of approximately 224 ml
blood. In PD patients and in healthy volunteers this is not associated with
risks. Insertion of arterial catheter can be painful. No immediate benefits for
the subjects are to be expected from participation in this study. However, an
indirect effect in the future is plausible for PD subjects, since more
knowledge about the pathophysiological mechanisms of the disease may lead to
improvement in therapy.
338, Gwanggyojungang-ro, Suji-gu, Yongin-si 338
Suji-gu, Yongin-si 338Gwanggyojungang-ro, Suji-gu, Yongin-si
KR
338, Gwanggyojungang-ro, Suji-gu, Yongin-si 338
Suji-gu, Yongin-si 338Gwanggyojungang-ro, Suji-gu, Yongin-si
KR
Listed location countries
Age
Inclusion criteria
- Participant understands the study procedures in the informed consent form and
is willing and able to comply with the study prescriptions
- Signed informed consent form
- Diagnosis of PD according to the Movement Disorder Society (MDS) clinical
diagnostic criteria (applicable to participants with Parkinson's Disease)
- Abnormal DAT-SPECT (applicable to participants with Parkinson's Disease)
- Age 40 years or older
- Medically healthy with no abnormalities at short neurological and physical
examination (applicable to healthy volunteers)
Exclusion criteria
- Inability to undergo MRI, e.g. metal objects in or around the body,
claustrophobia or inability to lie still in the scanner
- Inability to undergo PET-CT with administration of radioligand [18F]FB610,
including inability to lie still for 90 minutes.
- (History of) other relevant neurological disease
- (History of) malignancy
- Known significant cardiac disease
- Relevant history of severe drug allergy or hypersensitivity
- Inadequate renal function: creatinine clearance <60 ml/min
- Liver dysfunction: in male subjects ALAT >45 U/L and ASAT >35 U/L, in female
subjects ALAT >34 U/L and ASAT>31 U/L
- Loss or donation of blood over 500 mL within four months prior to study visits
- In male subjects Hb < 8.0 g/dL, in female subjects Hb < 7.0 g/dL
- Pregnancy or breast feeding
- Medications that, in the opinion of the PI or designee, may interfere with
the study, such as benzodiazepines. It is allowed for PD patients to use
dopaminergic medication.
- Exposure to previous radiation leading to an annual cumulative dose of more
than 10 mSV if participating in this protocol
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
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-002228-11-NL |
| CCMO | NL81730.029.22 |