Pharmacologically Modulating the Noradrenergic Arousal System to Reduce Freezing of Gait in Parkinson's Disease: a Multi-centre and Multi-modal Approach

Exclusion Criteria

• •Current and/or previous (within 3 months) participation in a clinical trial;
• •Any contra-indications for undergoing MRI-scanning (e.g. claustrophobia or metal parts within the body such as DBS, an infusion pump or a pacemaker);
• •Co-morbidity that significantly impacts ambulation (e.g. orthopaedic or rheumatological ailments);
• •Severe cognitive impairment hampering the ability to comply with the study protocol;
• •Active psychosis that would impact the ability to comply with the study protocol;
• •Severe cardiovascular disorders: severe hypertension (Sustained (Sitting) hypertension of ≥180 mmHg systolic or ≥110 mmHg diastolic, defined by the average of three observations, each at least 3 minutes apart, with the participant having assumed the required position for at least 3 minutes), heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias, long QT interval syndrome (QTc \> 500ms Bazett-formula) and channelopathies that in the opinion of the study PI would significantly compromise participant safety;
• •Severe cerebrovascular disorders: cerebral aneurysm or recent/significant stroke;
• •Hepatic or renal insufficiency that in the opinion of the Principal Investigator would impact on the ability of the participant to safely participate;
• •Narrow angle glaucoma;
• •(History of) pheochromocytoma;
• •Use of noradrenergic agents;
• •Use of CYP2D6 inhibitors (SSRIs, quinidine, terbinafine);
• •Use of high dose salbutamol (or other beta2 agonists) that in the opinion of the Principal Investigator would impact on the ability of the participant to safely participate;
• •Pregnancy and/or breastfeeding;
• •Known hypersensitivity to atomoxetine.