Pharmacologically modulating the noradrenergic arousal system to reduce freezing of gait in Parkinson’s disease: a multi-center and multi-modal approach.

Prior treatment

• Current and/or previous (within 3 months) participation in a clinical trial
• Use of CYP2D6 inhibitors (SSRIs, quinidine, terbinafine)

Other illness

• (History of) pheochromocytoma
• Known hypersensitivity to atomoxetine
• Severe cognitive impairment hampering the ability to comply with the study protocol
• Severe cerebrovascular disorders: cerebral aneurysm or recent/significant stroke
• Hepatic or renal insufficiency

Lab values

• 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 zettBa-formula) and channelopathies that would significantly compromise participant safety

Other

• Use of noradrenergic agents
• Use of high dose salbutamol (or other beta2 agonists)
• Pregnancy and/or breastfeeding
• 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)
• Active psychosis that would impact the ability to comply with the study protocol
• Narrow angle glaucoma

• Male or female aged 18 years or older
• Diagnosis of idiopathic Parkinson's disease according to Movement Disorders Society Diagnostic Criteria
• Stabilised on optimal dopaminergic treatment for a minimum of four weeks prior to the baseline visit (Visit 1)
• Presence of freezing of gait 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