Serotonin Release in Premotor and Motor PD

In this study, the investigators aim to provide a deeper understanding of Parkinson's disease and find a biomarker of Parkinson's disease. This is done using imaging scans called Positron Emission tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI). The findings will provide a deeper understanding of the brain changes in Parkinson's disease. More importantly, this study will help with the discovery and development of new medications aiming to delay progression of Parkinson's disease symptoms

The purpose of this study is to find a biomarker for Parkinson's disease (PD). A biomarker is an indicator of the presence of a disease, that can be measured, and that is able to give information about the progression, or severity, of it.

The study visits will take place in London. There are three locations on Hammersmith hospital campus, that are located near to each other. The NIHR Imperial Clinical Research Facility and Invicro London for clinical and MRI and PET assessments, and Imperial Healthcare Nuclear Medicine Department for the SPECT scan.

Participants will attend 5 visits in a 3 month period. These visits include an initial consent and assessment visit where some blood samples will also be taken. The second visit involves a PET scan with the tracer DASB along with an MRI scan. The third visit involves two PET scans one in the morning, with CIMBI tracer, an injection of Dexamphetamine, and then a second with CIMBI tracer to make a comparison. The fourth visit involves a SPECT scan, and the fifth visit is optional and would be for a lumbar puncture visit. Each visit will last around 6 hours.

Eligibility Criteria:
Inclusion criteria-

* Subjects must understand the nature of the study and must provide signed and dated written HRA-approved informed consent in accordance with local regulations before any protocol-specific screening procedures are performed;
* Males and females, age 25-85 years, inclusive;
* Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative β-hCG test at screening. For sexually active subjects (except females of non-childbearing potential-e.g., at least 2 years postmenopausal or surgically sterile), condoms should be used in addition to other birth control methods for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. These patients must be willing to remain on their current form of contraception for the duration of the study. All male subjects must agree to refrain from donating sperm for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. Sexually active male subjects must agree to use condoms to protect their partners from becoming pregnant for the duration of the study and for 3 months after the last administration of PET or SPECT ligands (i.e. for 15 consecutive months following baseline PET and SPECT scans); agree to ensure that they and their partners are routinely using a medically approved contraceptive method. It is important that male subjects not impregnate others for the duration of the study and for 3 months after the last administration of PET or SPECT ligands;
* Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures;
* Adequate visual and auditory acuity to complete the psychological testing;
* In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.

Exclusion criteria -

* Subjects lacking capacity according to investigator judgement;
* Subjects taking serotonin acting drugs such as antidepressants (i.e. tricyclic or selective serotonin reuptake inhibitors etc.);
* Pregnancy or breastfeeding or intent to become pregnant in the next 18 months;
* Subjects with current or a recent history of drug or alcohol abuse/dependence;
* Subjects who have other neurological disorders and known intracranial co-morbidities such as stroke, hemorrhage, 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 behaviour 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 and follow-up PET scans;
* Use of any oral corticosteroid within 30 days prior to baseline and follow-up PET scans;
* Use of metoclopramide within 30 days prior to baseline and follow-up (Day -1);
* Use of any thyroid medication within 30 days prior to baseline and follow-up (Day -1);
* Regular use (e.g., taken \> 3 days/week) of narcotic pain medications within 30 days prior to baseline and follow-up (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 modified Allen test in both hands, unless the brachial artery is used for arterial cannulation;
* Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable;
* History of severe skin allergy;
* 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;
* Initiation or change in pharmacologic therapy for symptoms of PD within 30 days prior to screen or between screen and baseline and follow-up (Day -1).
* GDS score greater than or equal to 10 (GDS score of 5 - 9 requires Investigator discretion to enter study).
* STAI Form Y-1 greater than or equal to 54 requires Investigator discretion to enter study.