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

Primary Purpose

Parkinson Disease, Autonomic Dysfunction, Depression

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

transcranial magnetic stimulation

About this trial

This is an interventional basic science trial for Parkinson Disease

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of North Carolina School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

medial prefrontal cortex - control site - dorsolateral prefrontal cortex

medial prefrontal cortex - dorsolateral prefrontal cortex - control site

dorsolateral prefrontal cortex - medial prefrontal cortex - control site

dorsolateral prefrontal cortex - control site - medial prefrontal cortex

control site - medial prefrontal cortex - dorsolateral prefrontal cortex

control site - dorsolateral prefrontal cortex - medial prefrontal cortex

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

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.

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT05205772

First Posted

December 2, 2021

Last Updated

April 12, 2023

Sponsor

University of North Carolina, Chapel Hill

1. Study Identification

Unique Protocol Identification Number

NCT05205772

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 1, 2022 (Actual)

Primary Completion Date

July 30, 2024 (Anticipated)

Study Completion Date

July 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease, Autonomic Dysfunction, Depression

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Participant

Masking Description

Participant will be blinded as to which site is being stimulated, experimental site or control site.

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

medial prefrontal cortex - control site - dorsolateral prefrontal cortex

Arm Type

Experimental

Arm Description

Arm Title

medial prefrontal cortex - dorsolateral prefrontal cortex - control site

Arm Type

Experimental

Arm Description

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.

Arm Title

dorsolateral prefrontal cortex - medial prefrontal cortex - control site

Arm Type

Experimental

Arm Description

Arm Title

dorsolateral prefrontal cortex - control site - medial prefrontal cortex

Arm Type

Experimental

Arm Description

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.

Arm Title

control site - medial prefrontal cortex - dorsolateral prefrontal cortex

Arm Type

Experimental

Arm Description

Arm Title

control site - dorsolateral prefrontal cortex - medial prefrontal cortex

Arm Type

Experimental

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

transcranial magnetic stimulation

Other Intervention Name(s)

intermittent theta-burst stimulation (iTBS)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in frontal midline theta EEG power after brain stimulation

Description

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).

Time Frame

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

Title

Superiority of stimulation at the medial prefrontal cortex and dorsolateral prefrontal cortex over stimulation at the control site

Description

Time Frame

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

Title

Correlation between the SCales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) total score and EEG

Description

Time Frame

At least 30 minutes before initial iTBS

Title

Correlation between the Orthostatic Hypotension Questionnaire (OHQ) and EEG

Description

Time Frame

At least 30 minutes before initial iTBS

Title

Correlation between degree of orthostatic hypotension and EEG

Description

Time Frame

At least 30 minutes before initial iTBS

Other Pre-specified Outcome Measures:

Title

SCOPA-AUT response to brain stimulation

Description

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

Time Frame

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

Title

OHQ response to brain stimulation

Description

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.

Time Frame

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

Title

Response of orthostatic blood pressure changes to brain stimulation

Description

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.

Time Frame

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

Title

Depression symptom response to brain stimulation

Description

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.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Miriam Sklerov, MD

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of North Carolina School of Medicine

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Miriam Sklerov, MD

Phone

984-974-4401

miri@email.unc.edu

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

IPD Sharing Time Frame

9 months to 36 months after publication.

IPD Sharing 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.

Learn more about this trial

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

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