Freezing of gait (FOG) is a burdensome Parkinson’s disease (PD) symptom. Gait control in people with PD relies on compensation from cognitive, sensory, and limbic networks. Their integration is influenced by the noradrenergic ascending arousal system, modulated by the locus coeruleus. In PD, locus coeruleus degeneration has been linked to increased FOG severity. Atomoxetine, a selective noradrenaline reuptake inhibitor, may provide a novel therapeutic approach for FOG. However, to date, studies on atomoxetine’s effect on FOG have been underpowered and inconsistent. This study will evaluate the effects of atomoxetine on FOG severity, both in the dopaminergic OFF- and ON-states. Moreover, we will assess its mode of action by examining its influence on brain network topology. Additionally, we will examine clinical and imaging markers to predict an individual’s treatment response. Sixty patients with frequent FOG will be recruited for a multi-centre, single-dose, double-blind, placebo-controlled, cross-over clinical trial. Assessments include clinimetrics, MDS-UPDRS III, gait assessments, pupillometry, and neuroimaging, conducted in the dopaminergic OFF- and ON-states. The primary outcome is FOG severity in the dopaminergic OFF-state, quantified based on the percentage of time spent frozen during gait assessments. Resting-state fMRI is conducted to assess network integration and segregation across brain regions and task-fMRI for revealing neural circuitry changes during FOG. Lastly, locus coeruleus and substantia nigra integrity will be assessed using structural MRI. This study will provide insights into the role of the noradrenergic ascending arousal system and potentially identify a novel pharmaceutical treatment pipeline for FOG in PD.