Effect of Dopamine on Specific Processing of Shame and Embarrassment in Parkinson's Disease (BioDopa)

Impact of Dopamine Replacement Therapy on Shame and Embarrassment-specific Processing and Its Clinical Relevance in Parkinson's Disease Patients

Shame and embarrassment are two self-conscious emotions frequently experienced by Parkinson's disease (PD) patients. Shame and embarrassment scores strongly correlate with patient's quality of life, anxiety and depression ratings. However, the neurobiology of shame and embarrassment in PD and the influence of dopaminergic replacement therapy (DRT) is poorly understood.

The aim of this study is to characterize how brain structures and neuronal networks involved in Parkinson's disease-related shame, non-Parkinson's disease related shame and neutral control scenarios, are modulated by dopaminergic replacement therapy. For this purpose, functional MRI and connectivity measures between the basal ganglia and shame-related network will be analyzed while PD patients will perform a shame-induction task during both ON- (i.e. during the effect of DRT) and OFF-DRT (i.e. during the withdrawal of DRT) conditions. Correlation with clinical measures will be made.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Behavioral: Assessments in ON and OFF levodopa state

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Vanessa Fleury, MD; Phone Number: +41223728337; Email: Vanessa.FleuryNissen@hcuge.ch

Study Locations

• Switzerland
  • Geneva, Switzerland, 1204
    • Recruiting
    • University Hospital, Geneva
    • Contact: Vanessa Fleury, MD; Phone Number: +41223728337; Email: Vanessa.FleuryNissen@hcuge.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

PD patients will be recruited from the outpatient movement disorder clinic of the Neurology Department at the Geneva University Hospital (HUG). Patients, who participated in previous studies and who are now followed up by private physicians, could also be contacted by trained members of the clinic/research staff to propose the study.

Flyers with a brief explanation of the project could also be distributed to the physicians to invite patients to consider participating and reach out to a staff member for further information.

Healthy controls will be recruited among the patients' spouses and through advertisement placed in the HUG and the University Medical Centre.

Description

Inclusion Criteria:

• Diagnosis of Parkinson's disease (PD) based on United Kingdom Parkinson's Disease Society Brain Bank Criteria
• Patients in the PD phase called "motor and non-motor fluctuations stage".

• Presence of motor and non-motor fluctuations are based on:

  1. For motor fluctuations: a score of 1 on item 4.1 and/or 1 on item 4.3 of the Movement Disorder Society Unified Parkinson's Disease Rating Scale IV
  2. For non-motor fluctuations: a score of 2 on item III of the Behavioral Assessment of Parkinson's Disease
• To be on dopaminergic replacement therapy.

Healthy controls:

subjects without any known central nervous system (CNS) lesion or CNS clinical signs on examination

Exclusion Criteria:

• Age greater than 80 years
• Dementia or mild cognitive impairment based on a score <26 on the MOCA
• Ongoing depression with suicidal ideation
• Any clinically meaningful non-stable renal, hepatic, cardiovascular, respiratory cerebrovascular disease or other serious progressive physical diseases
• Participating in a pharmacological study
• Any MRI contraindications
• Intolerable "OFF" states when the effects of the PD medication wear off (e.g., severe pain, anxiety, depression at the end of the dose or in the morning upon waking)
• Inability to provide informed consent (legal guardianship)
• Inability to speak or read French.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in BOLD activity in ON versus OFF state	Difference in brain Blood Oxygenation Level Dependent (BOLD) activity between ON-levodopa versus OFF-levodopa patients, as well as age-matched healthy controls during the imaginary ideation of PD-shame related scenarios, non-PD shame related scenarios as well as neutral scenarios.	fMRI at rest and during a shame induction task, 1 hour in ON state and 1 hour in OFF state

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Vanessa Fleury, MD, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 2, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: 2022-00760

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No