Apathy in Parkinson Disease TMS Study

NCT ID: NCT06087926

Last Updated: 2025-06-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2027-06-30

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Medial Prefrontal Cortex - Control Site

Participants first undergo transcranial magnetic stimulation to the medial prefrontal cortex. After a 3-week washout period, participants then undergo transcranial magnetic stimulation to the control site.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

Transcranial magnetic stimulation (or TMS) is a non-invasive form of brain stimulation in which a magnetic pulse is applied directly to the scalp. TMS is FDA approved for the treatment of depression and other neuropsychiatric disorders and is regularly used in neurologic and psychiatric research.

ITBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatment lasts approximately 3 minutes.

Control Site - Medial Prefrontal Cortex

Participants first undergo transcranial magnetic stimulation to the control site. After a 3-week washout period, participants then undergo transcranial magnetic stimulation to the medial prefrontal cortex.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

Transcranial magnetic stimulation (or TMS) is a non-invasive form of brain stimulation in which a magnetic pulse is applied directly to the scalp. TMS is FDA approved for the treatment of depression and other neuropsychiatric disorders and is regularly used in neurologic and psychiatric research.

ITBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatment lasts approximately 3 minutes.

Interventions

Transcranial Magnetic Stimulation (TMS)

Transcranial magnetic stimulation (or TMS) is a non-invasive form of brain stimulation in which a magnetic pulse is applied directly to the scalp. TMS is FDA approved for the treatment of depression and other neuropsychiatric disorders and is regularly used in neurologic and psychiatric research.

ITBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatment lasts approximately 3 minutes.

Intervention Type: DEVICE

Other Intervention Names

Intermittent Theta-Burst Stimulation (iTBS)

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Miriam Sklerov, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

UNC-Chapel Hill, Cassidy Lab

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Anita Frohlich, LL.M.

Role: CONTACT

frohlicha@neurology.unc.edu

919-843-6880

Miriam Sklerov, MD

Role: CONTACT

miri@email.unc.edu

984-974-4401

Facility Contacts

Monica Coudurier

Role: primary

Other Identifiers

K23MH132884

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-1829

Identifier Type: -

Identifier Source: org_study_id