Mapping Levodopa Effects on Cortico-basal Ganglia Circuit Function in Parkinson's Disease

NCT06240624 | Active Not Recruiting

• 1 other identifier: H-22010296
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) are involuntary movements caused by long-term treatment with dopaminergic replacement therapy (levodopa). During the cause of PD, most patients develop LID. In this study, the investigators plan to investigate how the cortico-basal-ganglia networks are affected in LID. The investigators will examine PD patients with and without LID as well as healthy age-matched controls using fMRI and PET. During the fMRI experiment, participants will perform a novel go-no task engaging both motor, emotional and reward brain networks. Patients will be scanned before and after intake of levodopa to study the dynamic effects of dopaminergic therapy. Furthermore, a dopamine transporter PET will be acquired to study the dopaminergic degeneration of the patients with PD.

Conditions

Parkinson Disease

Keywords

Levodopa-induced dyskinesia; Parkinson's disease; fMRI

Outcome Measures

Primary Outcomes (22)

• Percent Mean Change in Blood Oxygen-level Dependent (BOLD) Scores During Modified Go/No-Go Task

  For each participant and each run, we will create general linear models with 20 regressors of interest. The regressors are Motor: Right, Left, and No-Go trials Emotion: Happy, Neutral, Sad Reward: High/low reward, high/low loss All above regressors will be separately modeled for the high- and the low-reward context. We will add a linear time modulation to all regressors to model dynamic changes in activation over time.

  4 task runs of 10 minutes each

• Peak force

  Measured with grip-force response. The data will be smoothed and normalized to the individual maximum voluntary contraction.

  4 task runs of 10 minutes each

• Reaction time

  Measured with grip-force response.

  4 task runs of 10 minutes each

• Maximum slope

  Maximum value of first derivative of grip-force curve. Measured with grip-force response. The data will be smoothed and normalized to the individual maximum voluntary contraction.

  4 task runs of 10 minutes each

• Maximal negative slope

  Maximum negative value of first derivative of grip-force curve. Measured with grip-force response. The data will be smoothed and normalized to the individual maximum voluntary contraction.

  4 task runs of 10 minutes each

• Parkinson's disease severity

  Total Unified Parkinson's Disease Rating Scale (UPDRS) score (sum of all 4 subscores listed below, range 0-199, higher values = worse outcome), UPDRS-1 (Cognitive and mental disease severity, range 0-16, higher values = worse outcome), UPDRS-2 (disease severity in relation to activities of daily living, range 0-52, higher values = worse outcome) and UPDRS-3 (Motor severity, range 0-108, higher values = worse outcome), UPDRS-4 (Complications of therapy, range 0-23, higher values = worse outcome) subscores. Measured while subjects are taking their usual medication.

  Baseline (normal medication)

• Motor disease severity

  Unified Parkinson's Disease Rating Scale (UPDRS)-3 subscore (Motor severity, range 0-108, higher values = worse outcome). Measured while subjects are taking their usual medication. Unified Parkinson's Disease Rating Scale (UPDRS)-3 subscore (Motor severity, range 0-108, higher values = worse outcome). Measured while subjects are taking their usual medication. Unified Parkinson's Disease Rating Scale (UPDRS)-3 subscore (Motor severity, range 0-108, higher values = worse outcome). Measured while subjects are taking their usual medication.

  Before and 30-60 minutes after 150 % of normal morning levodopa dose as Madopar Quick.

• Non-motor disease severity

  Total Non-Motor Symptom Scale (NMSS) score (range 0-360, higher values = worse outcome). Measured while subjects are taking their usual medication.

  Baseline

• Non-motor fluctuation severity

  Total Non-Motor Fluctuation Assessment (NoMoFA) score (range 0-84, higher values = more severe non-motor fluctuations). Measured while subjects are taking their usual medication.

  Baseline

• Modified Hoehn and Yahr Staging

  Modified Hoehn and Yahr Staging (Crude measure of disease severity, range 0-5, higher score = worse outcome). Measured while subjects are taking their usual medication.

  Baseline

• Schwab and England Activities of Daily Living Scale

  Schwab and England Activities of Daily Living Scale (Measure of ADL function, range 100-0%, higher score = better ADL function). Measured while subjects are taking their usual medication.

  Baseline

• Apathy

  Total Lille Apathy Rating Scale (LARS) score (range -36-36, higher score = higher degree of apathy).

  Baseline

• Depression

  Major Depression Inventory (MDI) score (range 0-50), higher score = higher degree of depression

  Baseline

• Impulsive-Compulsive Disorders (ICD)

  Questionnaire for Impulsive-Compulsive Disorders (QUIP) (range 0-112), higher score = higher degree of ICD

  Baseline

• Cognitive function

  The Montreal Cognitive Assessment (MoCA) (range 0-30), higher score = better cognitive performance

  Baseline

• Impulsivity

  Barratt Impulsiveness Scale (BIS-11) (range 30-120), higher score = higher level of impulsivity.

  Baseline

• Dyskinesia severity

  Unified Dyskinesia Rating Scale (UDysRS)

  Baseline (usual medication intake) as well as before and 30-60 minutes after 150 % of normal morning levodopa dose as Madopar Quick (range 0-104), higher score = higher dyskinesia severity

• Dopaminergic degeneration

  Dopamine transporter (presynaptic) binding in the basal ganglia is measured using Fluorine-18 N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl) nortropane Positron Emission Tomography to

  Baseline

• Age

  Baseline

• Disease duration of Parkinson's disease

  Baseline

• Duration of levodopa-induced dyskinesia

  Baseline

• Medication

  Baseline

Study Arms (3)

Patients with Parkinson's disease and Levodopa-induced dyskinesia

Inclusion criteria: * Aged 18 or more * Clinically established or probable PD according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease * Peak-of-dose levodopa-induced dyskinesia * Stable antiparkinsonian medicine for 4 weeks * Signed informed consent Exclusion criteria: * Pregnancy or breastfeeding * History of other neurologic or psychiatric disease * Pacemaker or other implanted metallic or electronic devices which contraindicate MRI or TMS of the brain * Claustrophobia

Other: No intervention

Patients with Parkinson's disease without Levodopa-induced dyskinesia

Inclusion criteria: * Aged 18 or more * Clinically established or probable PD according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease * No levodopa-induced dyskinesia * Stable antiparkinsonian medicine for 4 weeks * Signed informed consent Exclusion criteria: * Pregnancy or breastfeeding * History of other neurologic or psychiatric disease * Pacemaker or other implanted metallic or electronic devices which contraindicate MRI or TMS of the brain * Claustrophobia

Other: No intervention

Healthy controls

Inclusion criteria: * Aged 18 or more * Age- and sex-matched the PD groups * Signed informed consent Exclusion criteria: * Pregnancy or breastfeeding * History of other neurologic or psychiatric disease * Pacemaker or other implanted metallic or electronic devices which contraindicate MRI or TMS of the brain * Claustrophobia

Other: No intervention

Interventions

No intervention OTHER

No intervention will be given.

Healthy controls; Patients with Parkinson's disease and Levodopa-induced dyskinesia; Patients with Parkinson's disease without Levodopa-induced dyskinesia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers, age- and sex-matched the PD groups

You may qualify if:

• Aged 18 or more

You may not qualify if:

• Pregnancy or breastfeeding
• History of other neurologic or psychiatric disease
• History of epilepsy or familiar dispositions of epilepsy
• Pacemaker or other implanted metallic or electronic devices which contraindicate MRI or TMS of the brain
• Claustrophobia

Sponsors & Collaborators

• Danish Research Centre for Magnetic Resonance: lead
• Bispebjerg Hospital: collaborator

Study Sites (1)

Danish Research Centre for Magnetic Resonance, Hvidovre Hospital

Hvidovre, Danmark, 2650, Denmark

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2023
• First Posted: February 5, 2024
• Study Start: August 15, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 22, 2025

Record last verified: 2025-03

Locations

DK (1)