Serotonin Release in Premotor and Motor PD

Exclusion Criteria27

• 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.