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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05205772
• Other study ID #: 21-0751
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2022
• Est. completion date: July 30, 2024

Study information

• Verified date: April 2023
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: July 30, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

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.

Related Conditions & MeSH terms

• Autonomic Dysfunction
• Autonomic Nervous System Diseases
• Depression
• Parkinson Disease
• Primary Dysautonomias

Intervention

Device:
• transcranial magnetic stimulation
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.

Locations

Country	Name	City	State
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SCOPA-AUT response to brain stimulation	Change in the SCales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) from 30 minutes before stimulation to 1 day after stimulation and 4 days after stimulation. 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	30 minutes pre-iTBS, and 1 day and 4 days after each iTBS treatment
Other	OHQ response to brain stimulation	Change in the Orthostatic Hypotension Questionnaire (OHQ) from before to after iTBS. The OHQ will be administered at least 30 minutes before stimulation, and again 1 day and 4 days after stimulation. The OHQ is an orthostatic hypotension symptom survey and 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.	At least 30 minutes pre-iTBS, and day 1 and day 4 after each iTBS treatment
Other	Response of orthostatic blood pressure changes to brain stimulation	Change in the orthostatic blood pressure change from before to after iTBS. Orthostatic vital signs will be measured 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. This will be measured at least 30 minutes before brain stimulation, and again 30 minutes after brain stimulation.	At least 30 minutes before each iTBS treatment, and 30 minutes after each iTBS treatment
Other	Depression symptom response to brain stimulation	Change in the Beck Depression Inventory II (BDI-II) from before to after iTBS. Participants will complete the BDI-II at least 30 minutes before brain stimulation. The questionnaire will be repeated 1 day and 4 days after stimulation. The BDI-II is a validated depression symptom survey. This survey contains 21 questions, with a score range of 0-63, where 0 means no depression symptoms and 63 indicates severe depression symptoms.	At least 30 minutes before each iTBS treatment, and day 1 and day 4 after each iTBS treatment
Primary	Change in frontal midline theta EEG power after brain stimulation	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).	At least 30 minutes before initial iTBS, and 30 minutes after each iTBS treatment
Primary	Superiority of stimulation at the medial prefrontal cortex and dorsolateral prefrontal cortex over stimulation at the control site	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.	At least 30 minutes before each iTBS treatment, and 30 minutes after each iTBS treatment
Primary	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 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.	At least 30 minutes before initial iTBS
Primary	Correlation between the Orthostatic Hypotension Questionnaire (OHQ) and EEG	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.	At least 30 minutes before initial iTBS
Primary	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 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.	At least 30 minutes before initial iTBS