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

Not Applicable

Completed

• Conditions: Depression; Parkinson Disease; Autonomic Dysfunction
• Interventions: Device: transcranial magnetic stimulation

• Registration Number: NCT05205772
• Lead Sponsor: University of North Carolina, Chapel Hill

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-12-02
• Study First Submitted QC: 2022-01-05
• Study First Posted: 2022-01-25
• Study Start: 2022-02-01
• Primary Completion: 2024-07-30
• Study Completion: 2024-07-30
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-22
• Last Update Posted: 2024-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• 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

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Exclusion Criteria

• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
medial prefrontal cortex - dorsolateral prefrontal cortex - control site	transcranial magnetic stimulation	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.
dorsolateral prefrontal cortex - medial prefrontal cortex - control site	transcranial magnetic stimulation	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.
dorsolateral prefrontal cortex - control site - medial prefrontal cortex	transcranial magnetic stimulation	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.
control site - dorsolateral prefrontal cortex - medial prefrontal cortex	transcranial magnetic stimulation	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.
medial prefrontal cortex - control site - dorsolateral prefrontal cortex	transcranial magnetic stimulation	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.
control site - medial prefrontal cortex - dorsolateral prefrontal cortex	transcranial magnetic stimulation	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.

Primary Outcome Measures

Name	Time	Method
Correlation between the Orthostatic Hypotension Questionnaire (OHQ) and EEG	At least 30 minutes before initial iTBS	Degree of correlation between the OHQ and frontal midline theta EEG power will be measured using regression analysis. The OHQ consists of two sections. The first is the orthostatic hypotension symptom assessment, which includes 6 questions with a score range of 0-66 (0 is no symptoms, 66 is most severe symptoms). The second part is 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 investigators will calculate the composite OHQ score, which is the average score between these two subsections.
Correlation between degree of orthostatic hypotension and EEG	At least 30 minutes before initial iTBS	Degree of correlation between degree of orthostatic hypotension and frontal midline theta EEG power will be measured using regression analysis. 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.
Change in frontal midline theta EEG power after brain stimulation	At least 30 minutes before initial iTBS, and 30 minutes after each iTBS treatment	Degree of change of frontal midline theta power on electroencephalography (EEG) after brain stimulation at each site (medial prefrontal cortex, dorsolateral prefrontal cortex, control site).
Superiority of stimulation at the medial prefrontal cortex and dorsolateral prefrontal cortex over stimulation at the control site	At least 30 minutes before each iTBS treatment, and 30 minutes after each iTBS treatment	Differences in the degree of change of frontal midline theta power on electroencephalography (EEG) after brain stimulation at each site (medial prefrontal cortex, dorsolateral prefrontal cortex, control site), determined by regression modeling.
Correlation between the SCales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) total score and EEG	At least 30 minutes before initial iTBS	Degree of correlation between the SCales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) total score and frontal midline theta EEG power will be measured using regression analysis. 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.

Trial Locations

Locations (1)

University of North Carolina School of Medicine; 🇺🇸 Chapel Hill, North Carolina, United States