Psychological Effects of Levodopa in Parkinson's Disease

NCT ID: NCT05119075

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-10
• Study Completion Date: 2024-03-31

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Dopaminergic ON-drug state first, dopaminergic OFF-drug state second

The following examinations and assessments will be performed at visit 3 on regular treatment in dopaminergic ON-drug state and at visit 4 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs):

• MRI assessment,
• Cognitive, neuropsychiatric and neurological assessment,
• Robot-induced hallucinations through sensorimotor stimulation.

Group Type: EXPERIMENTAL

Dopaminergic OFF-drug state

Intervention Type: OTHER

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

Intervention Type: OTHER

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.

Dopaminergic OFF-drug state first, dopaminergic ON-drug state second

The following examinations and assessments will be performed at visit 3 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs) and at visit 4 on regular treatment in dopaminergic ON-drug state:

• MRI assessment,
• Cognitive, neuropsychiatric and neurological assessment,
• Robot-induced hallucinations through sensorimotor stimulation.

Group Type: EXPERIMENTAL

Dopaminergic OFF-drug state

Intervention Type: OTHER

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

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

Ecole Polytechnique Fédérale de Lausanne

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Krack, Prof.

Role: PRINCIPAL_INVESTIGATOR

Insel Gruppe AG, University Hospital Bern

Locations

University Hospital Inselspital, Berne

Bern, , Switzerland

EPFL Campus Biotech

Geneva, , Switzerland

EPFL Institute of Bioengineering

Geneva, , Switzerland

University Hospital Geneva (HUG)

Geneva, , Switzerland

Countries

Switzerland

Other Identifiers

2021-01608

Identifier Type: -

Identifier Source: org_study_id