| Eligibility |
Inclusion Criteria:
All groups
- Women of child-bearing potential must use protocol-defined contraceptive measures and
must have a negative ß-hCG test at screening. For sexually active subjects (except
females of non-childbearing potential), condoms should be used in addition to other
birth control methods during the study, for 15 days after the last dose of
investigational drug, and for 3 months after the last administration of PET or SPECT
ligands. All male subjects must agree to refrain from donating sperm during the study,
for 15 days following the last dose of investigational drug, and for 3 months after
the last administration of PET or SPECT ligands. It is important that male subjects
not impregnate others while in the study.
- Adequate visual and auditory acuity to complete the psychological testing.
Idiopathic PD group
- Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society
Clinical Diagnostic Criteria (i.e. not induced by drugs or other diseases or carriers
of PD risk genes such as LRRK2, SNCA, PARK2 etc.).
- Hoehn and Yahr scale stage 1 or 2.
- Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or
on dopamine replacement therapy.
- Patients who have received the diagnosis of idiopathic PD within three years for
drug-naïve patients or within eight years for patients on dopamine replacement
therapy.
LRRK2 PD group
- Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society
Clinical Diagnostic Criteria and genetic confirmation of being carriers of LRRK2 PD
risk genes, diagnosed after the age of 30 years.
- Hoehn and Yahr scale stage 1 or 2.
- Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or
on dopamine replacement therapy.
- Patients who have received the diagnosis of idiopathic PD within three years for
drug-naïve patients or within eight years for patients on dopamine replacement
therapy.
Exclusion Criteria:
- Patients who had previous surgery for PD (including but not limited to deep brain
stimulation [DBS] or cell transplantation).
- Patients who are treated with duodopa or apomorphine.
- Patients taking serotonin acting drugs such as antidepressants (i.e. tricyclic or
selective serotonin reuptake inhibitors etc.)
- Patients taking drugs acting on SV2A such as antiepileptics (i.e. levetiracetam or
brivaracetam etc.)
- Pregnancy or breastfeeding.
- Patients with current or a recent history of drug or alcohol abuse/dependence.
- Patients who have other neurological disorders and known intracranial co-morbidities
such as stroke, haemorrhage, space-occupying lesions.
- Presence of any clinically significant medical condition (including cardiovascular,
respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or
other disease) that, based on the judgment of the investigator, is clinically
unstable, is likely to deteriorate during the course of the study, could put the
patient at risk because of participation in the study, could affect the subject's
ability to complete the study, or could influence the study results.
- History of suicidal behavior or active suicidal ideation.
- Within 1 year prior to screen or between screen and baseline (Day -1), any of the
following: myocardial infarction; hospitalization for congestive heart failure;
hospitalization for, or symptoms of, unstable angina; or syncope not related to PD.
- History or presence of renal disease or impaired renal function.
- Clinically important infection (e.g., chronic, persistent, or acute infection) within
30 days prior to screen or between screen and baseline (Day -1).
- History of cancer within the last 5 years, with the exception of nonmetastatic basal
cell carcinoma of the skin.
- Clinically significant blood clotting or bleeding disorder, including clinically
significant abnormal findings in laboratory assessments of coagulation or hematology.
- Use of antipsychotic medication within 3 months prior to screen or between screen and
baseline (Day -1).
- Use of any anticoagulant within 30 days prior to baseline PET scan.
- Use of any oral corticosteroid within 30 days prior to baseline PET scan.
- Use of metoclopramide within 30 days prior to baseline (Day -1).
- Use of any thyroid medication within 30 days prior to baseline (Day -1).
- Regular use (e.g., taken > 3 days/week) of narcotic pain medications within 30 days
prior to baseline (Day -1).
- Presence of any of the following MRI contraindications: pacemaker; cardiac
defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart
valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted
medical device (e.g., Swan-Ganz catheter, insulin pump); or metal fragments or foreign
objects in the eyes, skin, or body.
- Negative Allen test in both hands, unless the brachial artery is used for arterial
cannulation.
- Claustrophobia and history of back pain that makes prolonged laying on the PET or MRI
scanner intolerable.
- Initiation or change in pharmacologic therapy for symptoms of PD within 30 days prior
to screen or between screen and baseline (Day -1).
In addition, the following are exclusionary for subjects participating in CSF sampling:
- Any spinal malformations or other aspects (e.g., tattoos) or other clinical findings
(e.g., papilledema seen with ophthalmoscopy) that may complicate or contraindicate lumbar
puncture, as judged by the investigator.
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