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Blood Pressure Effects on Cognition and Brain Blood Flow in PD

Primary Purpose

Parkinson Disease, Orthostatic Hypotension, Dysautonomia

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Tilt table (upright position)
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Parkinson Disease

Eligibility Criteria

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

Inclusion Criteria:

  1. diagnosis of idiopathic Parkinson Disease using the Movement Disorders Society (MDS) Clinical Diagnostic Criteria
  2. age > 50 years old
  3. Hoehn & Yahr (H&Y) stages I-III (early to moderate-stage PD; able to walk without assistance
  4. proficiency in the English language (native English speaker level)

Exclusion Criteria:

  1. any involuntary movements (i.e., tremor or dyskinesia) > 3 cm in amplitude (ok if movements are treated with medication), since the motion artifact could interfere with blood pressure monitor data collection
  2. dementia (including PD dementia)
  3. status post deep brain stimulation (DBS)
  4. any unstable, active medical problem, e.g. decompensated heart failure, liver failure, etc.; 5) moderate or severe carotid artery stenosis (according to North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria)

6) history of cerebral infarction or hemorrhage 7) uncontrolled diabetes or any other systemic disease causing autonomic failure; 8) syncope (fainting) within the past week 9) illiteracy 10) taking antihypertensive medications or alpha-adrenergic blocking medications, since these can cause hypotension 11) impairment of hearing or vision that is not corrected by devices (e.g., hearing aids or glasses) 12) currently pregnant (will be confirmed by women of child-bearing potential with urine pregnancy test) 13) any other condition, which, in the opinion of the investigator, could place the participant at increased risk.

Please note that persons may not participate if they are taking any of the following:

  • medications to treat high blood pressure (called "antihypertensives") such as clonidine (Catapres), hydralazine, verapamil, diltiazem (Cartia), or medications ending in "-olol", "-artan", or "-pril")
  • diuretics (also called "water pills") such as furosemide (Lasix), bumetanide (Bumex), hydrochlorothiazide (HCTZ; Microzide), or spironolactone (Aldactone)
  • medications for enlarged prostate such as prazosin (Minipress), terazosin, doxazosin (Cardura), alfuzosin (Uroxatral), or tamsulosin (Flomax)

If persons are taking these medications and would like to participate in the study, they will be advised to discuss whether they may discontinue these medications for 48 hours before the study visit with their prescribing doctor.

Sites / Locations

  • University of California San DiegoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Supine cognitive testing first

Upright cognitive testing first

Arm Description

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) supine, 2) upright, 3) supine, 4) upright.

The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) upright, 2) supine, 3) upright, 4) supine.

Outcomes

Primary Outcome Measures

Delis-Kaplan Executive Function System Verbal Fluency Test score (number of words per minute). Minimum: 0; Maximum: N/A; higher is better
Participant says as many words in 1 minute as possible each of several letter or category prompts.
Oxygenated and deoxygenated hemoglobin change from baseline
Functional near-infrared spectroscopy will measure relative changes in oxygenated and deoxygenated hemoglobin variables

Secondary Outcome Measures

Full Information

First Posted
May 23, 2022
Last Updated
June 30, 2023
Sponsor
University of California, San Diego
Collaborators
Beth Israel Deaconess Medical Center, Drexel University
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1. Study Identification

Unique Protocol Identification Number
NCT05400174
Brief Title
Blood Pressure Effects on Cognition and Brain Blood Flow in PD
Official Title
Effects of Blood Pressure on Cognition and Cerebral Blood Flow in Parkinson Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2021 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
Collaborators
Beth Israel Deaconess Medical Center, Drexel University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Besides causing symptoms that impair movement, PD also causes non-motor symptoms, such as problems thinking and orthostatic hypotension (OH), i.e., low blood pressure (BP) when standing. About one-third of people with PD have OH, which can cause sudden, temporary symptoms while upright, including lightheadedness, dizziness, and fainting. People with PD and OH can also experience problems thinking that happen only while upright and not while sitting - this can occur without other symptoms, such as feeling dizzy or faint. However, the level of low BP that can affect thinking remains unknown, and no guidelines exist for treating OH when it happens without symptoms. This is significant because OH could be a treatable risk factor for thinking problems in PD, but OH is often not treated if people do not report obvious symptoms. This project's goal is to determine how BP affects brain function in PD. The proposed experiments will measure BP and brain blood flow continuously in real-time using innovative wearable technology. Persons with PD with OH and without OH will undergo repeated cognitive tests while supine (lying down) and while upright. I will study the associations between BP, thinking abilities, and brain blood flow, and will compare groups with and without OH. These findings could be important because if a certain level of BP correlates with thinking abilities, then treating OH in PD may prevent thinking problems, which would improve health-related quality of life and reduce disability and healthcare costs.
Detailed Description
After reviewing and signing an IRB-approved informed consent, participants will undergo the following clinical assessments for the Screening Visit (duration 3 hours), to determine eligibility: complete medical and surgical history including current medication and substance use general physical and neurological exam a tilt table test to confirm presence or absence of orthostatic hypotension (OH) OH (defined as systolic BP drop of > 20mmHg or diastolic BP drop of > 10mmHg within 3 minutes of head-up tilt, per consensus criteria (Gibbons et al., 2017) Orthostatic Hypotension Questionnaire (OHQ) (contains 6 items assessing OH symptoms and 4 items assessing OH symptom burden on daily activities) Movement Disorders Society Unified Parkinson's Disease Rating Scale Geriatric Depression Scale head circumference measurements to plan for optimal fitting of the functional near-infrared spectroscopy cap a reading test a cognitive test Baseline Study Visit Procedures: If participants meet all eligibility criteria, after undergoing the screening visit, they will later attend a baseline study visit (duration about 3 hours), which will occur on a separate day. Participants will be instructed to eat a small meal on the day of the visit, abstain from caffeine for 24 hours, and to take all home medications as prescribed. Participants will be encouraged to bring any prescribed antiparkinsonian medications with them to the study visit if it coincides with their usual dosing time, since fluctuations in dopaminergic medications could impact cognitive performance. Upon arrival, participants will complete the Orthostatic Hypotension Questionnaire (OHQ). Continuous Non-Invasive BP Monitoring: The CareTaker® is a Food and Drug Administration (FDA)-approved continuous, non-invasive, beat-to-beat BP monitor. This device is worn around the wrist like a watch and uses a sensor attached to an inflatable finger cuff to measure BP by detecting arterial pulsations beneath the skin. The device can continuously monitor BP for up to 24 hours in the ambulatory setting with wireless Internet connection. The CareTaker® uses Bluetooth technology to transmit BP data to a paired electronic Android tablet, automatically logging and documenting BP parameters and waveforms. Data can be accessed immediately on the tablet. variables that will be analyzed. At the start of the visit, the CareTaker® will be placed on the participant's hand that has the least involuntary movement, (e.g., tremor or dyskinesia) to minimize any motion artifact. The BP monitor will be worn during the entire visit and will be removed at the end of the visit. The start and end time of each cognitive task will be recorded and will be time- stamped with an event marker on the Caretaker® to correlate BP with each cognitive task. This study design was adapted from methods used by Centi et al. to study position-related cognitive changes in PD OH+ and OH-. In this study, participants will perform a cognitive battery while lying down and while upright on a tilt table. The clinical research coordinator will undergo training for all cognitive tests described and will administer the tests. The entire battery will take about 40 minutes and will be repeated twice; so the duration of cognitive testing is about 1 hour, 20 minutes. Each cognitive task will be administered twice: once while lying down and once while upright (at a 70 degree angle) on a tilt table. Cognitive testing will be split into four 20-minute sessions: two 20-minute sessions in the supine position and two 20-minute sessions in the upright position. The cognitive testing sessions will be alternated between supine and upright positions (i.e., supine, upright, supine, upright (Group A); or upright, supine, upright, supine (Group B). Participants will be randomized to Group A or Group B. After the upright testing sessions, the participant will be lowered to supine and will rest supine until systolic and diastolic BP returns to within 10mmHg of the baseline BP before beginning the supine cognitive testing. Cognitive tasks with visual components will be adapted to the supine and upright positions by using a projector to display the tests on a screen. After the testing, participants will be released from the tilt table, and the fNIRS and Caretaker® will be removed. Functional near-infrared spectroscopy (fNIRS) is a non-invasive, wearable technology that applies distinct near-infrared light wavelengths into the scalp to measure changes in the color of blood, since oxy- hemoglobin (HbO) absorbs light differently than deoxy-hemoglobin (Hb). Activation of neurons (e.g., in response to a cognitive task) increases brain tissue's metabolic demand, which increases regional cerebral blood flow, leading to increased HbO and decreased Hb. To detect these changes, fNIRS sources emit light, which are paired with light detectors to penetrate regions of brain cortex. Collectively, these probes are arranged in custom montages, which are worn on a head cap. Advantages unique to fNIRS are its safety, portability, and ability to study brain blood flow in different positions. The proposed research will use a 16-channel, 16-detector system, the NIRSport2 (NIRx®). During the supine and upright cognitive testing described above, participants will wear an fNIRS cap. Real-time cerebral oxygenation changes will be measured continuously throughout the study visit, including during cognitive tasks. We will collect baseline data for 30 seconds in each position before beginning cognitive testing. The continuous recordings from the fNIRS and the CareTaker® will be time synchronized. The start and end of each cognitive task will be time-stamped on the fNIRS to later correlate HbO and Hb changes with each cognitive task during data analysis. The fNIRS will be removed at the end of the visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Orthostatic Hypotension, Dysautonomia

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Supine cognitive testing first
Arm Type
Other
Arm Description
The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) supine, 2) upright, 3) supine, 4) upright.
Arm Title
Upright cognitive testing first
Arm Type
Other
Arm Description
The cognitive testing sessions will be alternated between supine and upright positions. This group will perform cognitive testing sessions in the following order: 1) upright, 2) supine, 3) upright, 4) supine.
Intervention Type
Diagnostic Test
Intervention Name(s)
Tilt table (upright position)
Other Intervention Name(s)
Cognitive testing battery
Intervention Description
Different versions of cognitive assessments will be administered in the supine and upright positions.
Primary Outcome Measure Information:
Title
Delis-Kaplan Executive Function System Verbal Fluency Test score (number of words per minute). Minimum: 0; Maximum: N/A; higher is better
Description
Participant says as many words in 1 minute as possible each of several letter or category prompts.
Time Frame
up to 30 months
Title
Oxygenated and deoxygenated hemoglobin change from baseline
Description
Functional near-infrared spectroscopy will measure relative changes in oxygenated and deoxygenated hemoglobin variables
Time Frame
up to 30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of idiopathic Parkinson Disease using the Movement Disorders Society (MDS) Clinical Diagnostic Criteria Age at least 50 years old Hoehn & Yahr (H&Y) stages I-III (early to moderate-stage PD; able to walk without assistance Proficiency in the English language (native English speaker level) Exclusion Criteria: Any involuntary movements (i.e., tremor or dyskinesia) > 3 cm in amplitude (ok if movements are treated with medication), since the motion artifact could interfere with blood pressure monitor data collection Dementia (including PD dementia) History of deep brain stimulation (DBS) surgery Any current unstable, active medical problem, e.g. decompensated heart failure, liver failure, pneumonia, etc. Moderate or severe carotid artery stenosis (according to North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria History of cerebral infarction or hemorrhage Uncontrolled diabetes or any other systemic disease causing autonomic failure Syncope (fainting) within the past week Illiteracy (unable to read) Taking antihypertensive medications or alpha-adrenergic blocking medications, since these can cause hypotension (see * below) Impairment of hearing or vision that is not corrected by devices (e.g., hearing aids or glasses) Currently pregnant (will be confirmed by women of child-bearing potential with a urine pregnancy test) Any other condition, which, in the opinion of the investigator, could place the participant at increased risk. Please note that persons may not participate if they are taking any of the following: medications to treat high blood pressure (called "antihypertensives") such as clonidine (Catapres), hydralazine, verapamil, diltiazem (Cartia), or medications ending in "-olol", "-artan", or "-pril") diuretics (also called "water pills") such as furosemide (Lasix), bumetanide (Bumex), hydrochlorothiazide (HCTZ; Microzide), or spironolactone (Aldactone) medications for enlarged prostate such as prazosin (Minipress), terazosin, doxazosin (Cardura), alfuzosin (Uroxatral), or tamsulosin (Flomax) If persons are taking these medications and would like to participate in the study, they will be advised to discuss whether they may discontinue these medications for 48 hours before the study visit with their prescribing doctor.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine Longardner, MD
Phone
8582462579
Email
klongardner@health.ucsd.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Skipworth, BS
Email
mskipworth@health.ucsd.edu
Facility Information:
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katherine Longardner, MD
Phone
614-439-7427
Email
klongardner@ucsd.edu
First Name & Middle Initial & Last Name & Degree
Michael Skipworth, BS
Ext
Longardner
Email
klongardner@health.ucsd.edu
First Name & Middle Initial & Last Name & Degree
Katherine Longardner, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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Citation
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Blood Pressure Effects on Cognition and Brain Blood Flow in PD

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