Investigating the Causal Role of preSMA in Levodopa-induced Dyskinesia in Parkinson's Disease
Targeting the Pre-supplementary Motor Area With Repetitive Transcranial Magnetic Stimulation to Alleviate Levodopa-induced Dyskinesia in Parkinson´s Disease
1 other identifier
interventional
20
1 country
1
Brief Summary
Using a within-subject cross-over design, we will include 20 patients with Parkinson disease (PD) and peak-of-dose dyskinesia. Patients will be studied after withdrawal from their normal dopaminergic medication. On two separate days, each patient will receive off-line, effective (high-intensity) or ineffective (low-intensity) 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the presupplementary motor area (preSMA) before functional magnetic resonance (fMRI). Immediately after the patient will perform a Go/No-Go task during fMRI in the the OFF state for 9 minutes. Then the scan is paused and the patient will receive 200 mg fast-acting oral levodopa and undergo whole-brain task-related fMRI at 3 Tesla until peak-of-dose dyskinesia will emerge. During task-related fMRI, patients has to click on a mouse with their right hand (Right-Go), left hand (Left-Go), or no action (No-Go) in response to arbitrary visual cues. The patients will also be tested for different aspects of impulsivity using neuropsychological questionnaires and computerized tests.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Aug 2017
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 1, 2017
CompletedStudy Start
First participant enrolled
August 1, 2017
CompletedFirst Posted
Study publicly available on registry
November 28, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 16, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 16, 2018
CompletedAugust 6, 2019
August 1, 2018
1.1 years
June 1, 2017
August 3, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Levodopa-induced change in task-related regional neural activity as indexed by the blood oxygen level dependent (BOLD) signal
A single priming session of REAL rTMS over the preSMA will attenuate the abnormal pharmacodynamic BOLD response (which is an index of regional neural activity) in the cortico-basal ganglia loop after levodopa challenge compared with SHAM rTMS.
Within the first 60 minutes after levodopa intake
Secondary Outcomes (2)
Onset of LID
Within the first 60 minutes after levodopa intake
Severity of LID
Within the first 60 minutes after levodopa intake
Study Arms (2)
REAL TMS
EXPERIMENTAL30 minutes of repetitive transcranial magnetic stimulation with 100% of the patients' individual resting motor threshold.
SHAM TMS
SHAM COMPARATOR30 minutes of repetitive transcranial magnetic stimulation with 30% of the patients' individual resting motor threshold.
Interventions
Frequency: 1 Hz., Pulse shape: biphasic, Duration: 30 minutes (1800 pulses). Neuronavigation: MRI-guided and robot-assisted neuronavigation using Localite software and an Axilum robot.
Eligibility Criteria
You may qualify if:
- Clinical diagnosis of Parkinson's Disease (Hoehn \& Yahr 1-3)
- Peak-of-dose levodopa-induced dyskinesia
You may not qualify if:
- Insufficient Danish language skills
- Neurological disease other than Parkinson's Disease
- Major psychiatric illness
- Sedatives or serotonergic medication in their current treatment.
- Severe tremor
- Montreal Cognitive Assessment score \< 26
- Contraindication for transcranial magnetic stimulation:
- Epilepsy or epilepsy in 1st degree relatives
- Contraindications for MRI-scanning:
- Pacemaker
- Pregnancy
- Metallic foreign objects inside the body
- Severe claustrophobia
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Danish Research Centre for Magnetic Resonance
Hvidovre, Capital Region, 2650, Denmark
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hartwig R Siebner, MD, DMSci
Danish Research Centre for Magnetic Resonance
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Masking Details
- Sham stimulation
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 1, 2017
First Posted
November 28, 2017
Study Start
August 1, 2017
Primary Completion
September 16, 2018
Study Completion
September 16, 2018
Last Updated
August 6, 2019
Record last verified: 2018-08