Psychological Effects of Levodopa in Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05119075
• Other study ID #: 2021-01608
• Status: Recruiting
• Phase: N/A
• Start date: November 10, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2023
• Source: University Hospital Inselspital, Berne
• Contact: Paul Krack, Prof.
• Phone: 031 632 21 68
• Email: paul.krack[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 31, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Switzerland	University Hospital Inselspital, Berne	Bern
Switzerland	EPFL Campus Biotech	Geneva
Switzerland	EPFL Institute of Bioengineering	Geneva
Switzerland	University Hospital Geneva (HUG)	Geneva

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Ecole Polytechnique Fédérale de Lausanne, University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations	Score on the Neuropsychiatric Fluctuations Scale (NFS)	= 6 weeks
Primary	Correlation of functional connectivity abnormalities with shame	Score on the Shame Visual Analogic Scale	= 6 weeks
Primary	Correlation of functional connectivity abnormalities with hallucinations	Score on robot-induced presence hallucination (PH) ratings	= 6 weeks
Primary	Correlation of functional connectivity abnormalities with bradyphrenia	Score on the Bradyphrenia Scale	= 6 weeks
Primary	Correlation of functional connectivity abnormalities with creativity	Score on the Creative Thinking Scale	= 6 weeks
Secondary	The role of dopamine on hallucinations	Measurement of the influence of dopamine on hallucinations using the robot-induced presence hallucination (PH) ratings. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more hallucinations are experienced by patients.	= 6 weeks
Secondary	The role of dopamine on creativity	Measurement of the influence of dopamine on the Creative Thinking Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more creative the patients are.	= 6 weeks
Secondary	The role of dopamine on shame	Measurement of the influence of dopamine on the Shame Visual Analogic Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more shame patients feel.	= 6 weeks
Secondary	The role of dopamine on bradyphrenia	Measurement of the influence of dopamine on the bradyphrenia scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more bradyphrenic the patients are.	= 6 weeks