Clinical trial NCT06087926: Apathy in Parkinson Disease TMS Study
Official title: Investigation of Non-invasive Brain Stimulation for the Treatment of Apathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Apathy
Motivation
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2023-10-18
Enrollment: 60
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this clinical trial is to develop non-invasive brain stimulation targets for the treatment of apathy, or motivation problems, in Parkinson Disease.

The main questions the study aims to answer are:

1. Does transcranial magnetic stimulation change effort task performance in Parkinson's Disease patients?
2. Is there a link between brain signals and apathy?

Participants will

* complete questionnaires and assessments
* perform an effort task
* have their brain activity recorded (EEG)
* receive non-invasive brain stimulation (TMS)

Researchers will compare two stimulation locations (experimental site and control site) to see if TMS of the experimental site has an effect on apathy. Participants will receive stimulation of both sites (during separate visits).

Detailed description: Participants will be asked to come for 3 study visits.

During visit 1, after being informed about the study and potential risks, all patients giving written informed consent will undergo a brief cognitive assessment, a movement examination, and answer questionnaires. Additionally, the individual motor threshold will be determined for each participant. Visit 1 will take 2-3 hours.

Visits 2 and 3 will involve:

* completing questionnaires,
* performing a task where fictitious rewards can be earned by squeezing a dynamometer,
* recording brain activity with an electroencephalogram (EEG), and
* receiving transcranial magnetic stimulation (TMS). Visits 2 and 3 will take approximately 3 hours each and will be separated from each other by at least 3 weeks.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson Disease.
* At least 5 years of symptoms.
* On dopaminergic medication for Parkinson Disease.
* Stable on dopaminergic medication and other medications which may influence apathy (such as selective serotonin re-uptake inhibitors, stimulant medications) for at least 4 weeks prior to first study visit and remain stable throughout the study period.
* Hospital's study-specific informed consent must be obtained.
* Must have capacity to provide informed consent in English.
* For female participants, confirmation that they have not had a menstrual period in over 12 months, or that they will use an effective form of contraception during the study.

Exclusion Criteria:

* Inability to provide informed consent.
* Inability to perform effort task (determined during the titration session).
* Presence of dementia (Montreal Cognitive Assessment (MoCA) score \< 21).
* History of epilepsy or brain surgery.
* Severe tremor or dyskinesia that would interfere with EEG (determined by the PI).
* Patients with clinically significant medical or neurological conditions which may be an alternative cause of parkinsonism such as repeated brain injury, anti-dopaminergic medications, anoxic brain injury, or significant basal ganglia strokes.
* Presence of other known central nervous system disease that may interfere with performance or interpretation of EEG or TMS.
* Presence of any implanted metal devices including, but not limited to, pacemakers, deep brain stimulators, vagal nerve stimulators, bladder stimulators, or cochlear implants.
* Presence of medical contraindications to TMS such as implanted stimulators, history of mania or bipolar disorder, history of epilepsy.

Primary outcomes:
measure: Change in goal-directed behavior after transcranial magnetic stimulation (TMS)
timeFrame: Immediately before stimulation and 15 minutes after stimulation.
measure: Change in reward evaluation after transcranial magnetic stimulation (TMS)
timeFrame: Immediately before stimulation and 15 minutes after stimulation.
Secondary outcomes:
measure: Association between frontal midline theta EEG power and goal-oriented behavior
timeFrame: Approximately 45 minutes before and 45 minutes after stimulation.
measure: Association between frontal midline theta EEG power and reward evaluation
timeFrame: Approximately 45 minutes before and 45 minutes after stimulation.
Other outcomes:
measure: Association between frontal midline theta EEG power and subjective apathy
timeFrame: Approximately 45 minutes before and 45 minutes after stimulation.
Locations:
city: Chapel Hill
country: United States
facility: UNC-Chapel Hill, Cassidy Lab
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Miriam Sklerov, MD
role: PRINCIPAL_INVESTIGATOR
References: