Investigating Central Neurophysiologic Correlates of Non-Motor Symptoms of Parkinson's Disease

NCT05205772 | Completed Results FDA Device

• 1 other identifier: 21-0751
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, single-blinded, triple crossover study focused on determining the feasibility of using transcranial magnetic stimulation (TMS) for treatment of Parkinson's disease related autonomic dysfunction and depression. Participants will undergo TMS to three brain regions: medial prefrontal cortex (mPFC) (experimental site), dorsolateral prefrontal cortex (DLPFC) (alternative experimental site), or primary sensory cortex (S1) (control site) in a triple crossover design. Participants will complete symptom questionnaires, neurologic examination and cognitive assessments, and orthostatic vital signs recording before and after each brain stimulation session.

Conditions

Parkinson Disease; Autonomic Dysfunction; Depression

Outcome Measures

Primary Outcomes (4)

• Change in Frontal Midline Theta EEG Power After Brain Stimulation

  Degree of change of frontal midline theta (FMT) power on electroencephalography (EEG) after brain stimulation at each site (medial prefrontal cortex, dorsolateral prefrontal cortex, control site).

  At least 30 minutes before initial iTBS, and 30 minutes after each iTBS treatment

• Correlation Between the Scales for Outcomes in Parkinson's Disease - Autonomic (SCOPA-AUT) Total Score and EEG

  Degree of correlation between the Scales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) total score and frontal midline theta EEG power extracted from Baseline pre-stimulation initial visit EEG and SCOPA-AUT questionnaire. The SCOPA-AUT is a validated autonomic symptom survey for people with Parkinson's disease. It contains 6 domains (gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillary, and sexual). The investigators will use the total composite score including all domains. The score range is 0-69, with a total of 23 questions. 0 means no symptoms, 69 is highest burden of symptoms. The FMT and SCOPA-AUT were assessed at baseline. FMT power and SCOPA-AUT were correlated using the Spearman Correlation Coefficient calculation. A positive correlation coefficient indicates a positive relationship between the assessments; higher FMT power correlates with higher symptom burden.

  At least 30 minutes before initial iTBS

• Correlation Between the Orthostatic Hypotension Questionnaire (OHQ) and EEG

  Degree of correlation between the Orthostatic Hypotension Questionnaire (OHQ) composite score and frontal midline theta EEG power extracted from Baseline pre-stimulation initial visit EEG and OHQ questionnaire. The OHQ consists of two sections: 1-orthostatic hypotension symptom assessment, which includes 6 questions with a score range of 0-66 (0 is no symptoms, 66 is most severe symptoms); and 2-the orthostatic hypotension daily activity scale, which rates interference of symptoms on activities of daily living. This part consists of four questions, and score range is 0-44 (0 is no interference, 44 is most severe interference). The composite OHQ score is the average score between these two subsections. FMT power and OHQ were correlated using the Spearman Correlation Coefficient calculation. A positive correlation coefficient indicates a positive relationship between the assessments; higher FMT power correlates with higher symptom burden.

  At least 30 minutes before initial iTBS

• Correlation Between Degree of Orthostatic Hypotension and EEG

  Degree of correlation between degree of orthostatic hypotension and frontal midline theta EEG power will be measured extracted from Baseline pre-stimulation visit EEG and blood pressure measures. Orthostatic vital signs will be measured at least 30 minutes before initial iTBS as follows: blood pressure will be measured after at least 3 minutes of rest in the supine position. Blood pressure will again be measured after 3 minutes of standing. Blood pressure reduction is expressed as the magnitude of reduction, thus a positive number reflects a greater reduction. Lack of blood pressure reduction was coded as '0'. A positive correlation coefficient indicates a positive relationship between the assessments; higher FMT power correlates with higher more severe orthostatic hypotension.

  At least 30 minutes before initial iTBS

Other Outcomes (4)

• SCOPA-AUT Response to Brain Stimulation

  30 minutes pre-iTBS, and 1 day and 4 days after each iTBS treatment

• OHQ Response to Brain Stimulation

  At least 30 minutes pre-iTBS, and day 1 and day 4 after each iTBS treatment

• Response of Orthostatic Blood Pressure Changes to Brain Stimulation

  At least 30 minutes before each iTBS treatment, and 30 minutes after each iTBS treatment

Study Arms (6)

medial prefrontal cortex - control site - dorsolateral prefrontal cortex

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. After a 3 week washout period, participants undergo transcranial magnetic stimulation to the dorsolateral prefrontal cortex.

Device: transcranial magnetic stimulation

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

Device: transcranial magnetic stimulation

dorsolateral prefrontal cortex - medial prefrontal cortex - control site

EXPERIMENTAL

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

Device: transcranial magnetic stimulation

dorsolateral prefrontal cortex - control site - medial prefrontal cortex

EXPERIMENTAL

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

Device: transcranial magnetic stimulation

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

Device: transcranial magnetic stimulation

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

Device: transcranial magnetic stimulation

Interventions

transcranial magnetic stimulation 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. This device is FDA approved for 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 very quickly). 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 treatments lasts approximately 3 minutes.

Also known as: intermittent theta-burst stimulation (iTBS)

control site - dorsolateral prefrontal cortex - medial prefrontal cortex; control site - medial prefrontal cortex - dorsolateral prefrontal cortex; dorsolateral prefrontal cortex - control site - medial prefrontal cortex; dorsolateral prefrontal cortex - medial prefrontal cortex - control site; medial prefrontal cortex - control site - dorsolateral prefrontal cortex; medial prefrontal cortex - dorsolateral prefrontal cortex - control site

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between 50 and 90 years of age, without a diagnosis of severe dementia
• Carry a diagnosis of idiopathic Parkinson's disease based on the United Kingdom Parkinson's Disease Society Brain Bank clinical diagnostic criteria
• Have had symptoms of Parkinson's disease for at least 3 years
• Hospital's study-specific informed consent must be obtained
• Must have capacity to provide informed consent in English
• For female participants, confirmation that a menstrual period has not occurred in over 12 months, or that an effective form of contraception will be used during the study

You may not qualify if:

• Inability to provide informed consent.
• Severe dementia
• History of epilepsy or brain surgery
• Severe tremor or dyskinesia that would interfere with EEG as determined by the PI
• Parkinson's patients with clinically significant medical or neurological conditions which may be an alternative cause of orthostatic hypotension, such as neuropathy, renal failure, heart failure, cardiac arrhythmias, severe diabetes, or spinal cord injuries
• The investigators will exclude patients who are treated with medications which can significantly lower blood pressure or heart rate, such as antihypertensive medications, diuretics, and alpha-blocking medications
• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Primary Dysautonomias; Depression

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; Autonomic Nervous System Diseases; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Miriam Sklerov, MD, MS
• Organization: University of North Carolina at Chapel Hill

miri@email.unc.edu

984-974-4401

Study Officials

• Miriam Sklerov, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: December 2, 2021
• First Posted: January 25, 2022
• Study Start: February 1, 2022
• Primary Completion: July 30, 2024
• Study Completion: July 30, 2024
• Last Updated: May 21, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 9 months to 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)