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

Inclusion criteria

• Aged 18 years or older;
• Diagnosis of idiopathic PD according to MDS Diagnostic Criteria;
• Stabilised on optimal dopaminergic PD treatment for a minimum of four weeks prior to the baseline visit (Visit 1) and for the duration of the trial;
• Presence of FOG symptoms on a daily basis;
• Ability to walk for 10-meters unaided in the dopaminergic ON-state;
• Ability to provide written informed consent in accordance with ICH-GCP and local regulations;
• Willing and able to undergo all clinical trial assessments.

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.