Apathy in Parkinson Disease TMS Study

NCT06087926 | Recruiting FDA Device

• 2 other identifiers: 23-1829K23MH132884
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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:

• 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).

Conditions

Parkinson Disease

Keywords

Apathy; Motivation

Outcome Measures

Primary Outcomes (2)

• Change in goal-directed behavior after transcranial magnetic stimulation (TMS)

  Differences in the degree of change in goal-directed behavior after brain stimulation at each site (medial prefrontal cortex or control site). Goal-directed behavior will be determined using the streamlined version of the Expenditure of Effort for Reward Task (S-EEfRT). In the S-EEfRT, participants choose to complete either a "Hard" task or an "Easy" task for variable monetary incentives.

  Immediately before stimulation and 15 minutes after stimulation.

• Change in reward evaluation after transcranial magnetic stimulation (TMS)

  Differences in the degree of change in reward evaluation after brain stimulation at each site (medial prefrontal cortex or control site). Reward evaluation will be determined using the streamlined version of the Expenditure of Effort for Reward Task (S-EEfRT). In the S-EEfRT, participants choose to complete either a "Hard" task or an "Easy" task for variable monetary incentives.

  Immediately before stimulation and 15 minutes after stimulation.

Secondary Outcomes (2)

• Association between frontal midline theta EEG power and goal-oriented behavior

  Approximately 45 minutes before and 45 minutes after stimulation.

• Association between frontal midline theta EEG power and reward evaluation

  Approximately 45 minutes before and 45 minutes after stimulation.

Other Outcomes (1)

• Association between frontal midline theta EEG power and subjective apathy

  Approximately 45 minutes before and 45 minutes after stimulation.

Study Arms (2)

Medial Prefrontal Cortex - Control Site

EXPERIMENTAL

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.

Device: Transcranial Magnetic Stimulation (TMS)

Control Site - Medial Prefrontal Cortex

EXPERIMENTAL

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.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) 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.

Also known as: Intermittent Theta-Burst Stimulation (iTBS)

Control Site - Medial Prefrontal Cortex; Medial Prefrontal Cortex - Control Site

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UNC-Chapel Hill, Cassidy Lab

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Miriam Sklerov, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anita Frohlich, LL.M.

CONTACT

919-843-6880; frohlicha@neurology.unc.edu

Miriam Sklerov, MD

CONTACT

984-974-4401; miri@email.unc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant will be blinded as to which site is being stimulated, experimental site or control site.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2023
• First Posted: October 18, 2023
• Study Start: May 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: June 19, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 and continuing for 36 months after publication.
• Access Criteria: Data will be made available to investigators who have approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)