Apathy in Parkinson Disease TMS Study

Parkinson Disease Clinical Trial

— PDTMSAPATHY  

Official title:

Investigation of Non-invasive Brain Stimulation for the Treatment of Apathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06087926
• Other study ID #: 23-1829
• Secondary ID: K23MH132884
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: May 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Anita Frohlich, LL.M.
• Phone: 919-843-6880
• Email: frohlicha[@]neurology.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• 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.

Locations

Country	Name	City	State
United States	UNC-Chapel Hill, Cassidy Lab	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Association between frontal midline theta EEG power and subjective apathy	Degree of association between frontal midline theta EEG power and subjective apathy as measured with the Lille Apathy Rating Scale (LARS).; The LARS has been validated in Parkinson Disease. It consists of a structured interview that includes 33 items. Responses are scored on a dichotomous scale. The LARS score will be investigated as an effect measure modifier in the association between performance on the S-EEfRT and frontal midline theta power.	Approximately 45 minutes before and 45 minutes after stimulation.
Primary	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.
Primary	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	Association between frontal midline theta EEG power and goal-oriented behavior	Degree of association between frontal midline theta EEG power and goal-oriented behavior.; 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.	Approximately 45 minutes before and 45 minutes after stimulation.
Secondary	Association between frontal midline theta EEG power and reward evaluation	Degree of association between frontal midline theta EEG power and reward evaluation.; 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.	Approximately 45 minutes before and 45 minutes after stimulation.