NCT05119075

Psychological Effects of Levodopa in Parkinson's Disease

Unravelling the Impact of Levodopa on Dysfunctional Brain Networks in Parkinson's Disease With Neuropsychiatric Fluctuations

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Insel Gruppe AG, University Hospital Bern · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The investigators aim is to study neuropsychiatric symptoms and underlying abnormalities in resting-state fMRI in patients with Parkinson's disease (PD) suffering from neuropsychiatric fluctuations, to enhance the understanding of the pathophysiological mechanisms underlying neuropsychiatric symptoms.

Detailed description

Parkinson's disease (PD) is primarily classified and known as a movement disorder characterized by tremor, bradykinesia and rigidity. However, clinical examination and research have shown that PD extensively affects other systems as well, giving rise to non-motor symptoms (NMS) such as anxiety, sleep disorders, apathy, depression, cognitive impairment, and hallucinations. These non-motor fluctuations (NMF) represent a main source of disability in PD and among those, neuropsychiatric fluctuations are the most frequent. During the dopaminergic OFF-drug state anxiety, apathy, and depression are common, whereas during the dopaminergic ON-drug state euphoria, well-being, impulse control disorders (ICD) and other behavioral addictions, mania, and psychosis might occur. Despite the severe consequences associated with dopaminergic modulation, the understanding of the pathophysiological mechanisms of neuropsychiatric symptoms is still limited and better detection and more effective treatments are needed. Fluctuating PD is a very powerful model allowing to study opposite psychiatric states intra-individually in both levodopa dopaminergic ON- and OFF-drug state, allowing to abstract many interpersonal variables. Neurotechnology and advanced neuroimaging techniques can improve the understanding of the neural basis and brain mechanisms of specific neuropsychiatric symptoms in PD. In particular, dynamic functional connectivity (FC) analysis characterizes functional abnormalities from resting state (rs)-fMRI not only in terms of brain activations, but also of whole-brain functional networks and the transitions between maps of activations. The temporal evolution of these networks, assessed with dynamic FC approaches, has recently shown to be relevant in several clinical contexts. Therefore, the investigators long-term goal is to identify specific resting-state signatures/biomarkers for the individual neuropsychiatric PD symptoms related to disease in dopaminergic OFF-drug state (depression, anxiety, apathy, fatigue, shame, bradyphrenia) and to dopaminergic treatment in dopaminergic ON-drug state (mania, impulse control disorders, hallucinations, psychosis, creative thinking), which might be used in the future as a proxy for the measurement of neuropsychiatric symptoms/fluctuations and thus to assess the effectiveness of specific therapies.

Conditions

• Parkinson Disease

Interventions

Type	Name	Description
OTHER	Dopaminergic OFF-drug state	Dopaminergic OFF-drug state: Overnight withdrawal of dopaminergic antiparkinsonian drugs during visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.
OTHER	Dopaminergic ON-drug state	Dopaminergic ON-drug state: Patient will be evaluated in his/her regular treatment in dopaminergic ON-drug state at visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.

Timeline

• Start date: 2021-11-10
• Primary completion: 2024-03-31
• Completion: 2024-03-31
• First posted: 2021-11-12
• Last updated: 2025-04-13

Locations

4 sites across 1 country: Switzerland