Clinical trial NCT05119075: Psychological Effects of Levodopa in Parkinson's Disease
Official title: Unravelling the Impact of Levodopa on Dysfunctional Brain Networks in Parkinson's Disease With Neuropsychiatric Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Keywords: Neuropsychiatric fluctuations
Creativity
Shame
Embarrassment
Non-motor symptoms
Hallucinations
Bradyphrenia
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: Ecole Polytechnique Fédérale de Lausanne
First posted: 2021-11-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Adults above 18 years old
* Male or female
* Diagnosed with Parkinson's disease
* Able to understand instructions, neuropsychological tests and provide written informed consent
* Able to understand the locally used language of the experimental site and speak fluently
* Presence of neuropsychiatric fluctuations, defined as the sum ≥ 3 of items included in the Ardouin Scale of Behaviour in Parkinson's Disease (ASBPD) part 2

Exclusion Criteria:

* Structural brain disease other than Parkinson's disease
* Substance abuse and/or dependence (other than DRT)
* Ongoing depression with suicidal ideation
* Severe tremors/dyskinesia/ interfering with MRI performance
* Participating in a pharmacological study
* Inability to provide informed consent (legal guardianship)
* MRI contraindications
* Pregnancy

Primary outcomes:
measure: Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations
timeFrame: ≤ 6 weeks
measure: Correlation of functional connectivity abnormalities with shame
timeFrame: ≤ 6 weeks
measure: Correlation of functional connectivity abnormalities with hallucinations
timeFrame: ≤ 6 weeks
measure: Correlation of functional connectivity abnormalities with bradyphrenia
timeFrame: ≤ 6 weeks
measure: Correlation of functional connectivity abnormalities with creativity
timeFrame: ≤ 6 weeks
Secondary outcomes:
measure: The role of dopamine on hallucinations
timeFrame: ≤ 6 weeks
measure: The role of dopamine on creativity
timeFrame: ≤ 6 weeks
measure: The role of dopamine on shame
timeFrame: ≤ 6 weeks
measure: The role of dopamine on bradyphrenia
timeFrame: ≤ 6 weeks
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital Inselspital, Berne
city: Geneva
country: Switzerland
facility: EPFL Campus Biotech
city: Geneva
country: Switzerland
facility: EPFL Institute of Bioengineering
city: Geneva
country: Switzerland
facility: University Hospital Geneva (HUG)
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Paul Krack, Prof.
role: PRINCIPAL_INVESTIGATOR
References: