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NC Testing in LC & POTS

Primary Purpose

Postural Orthostatic Tachycardia Syndrome, Post Acute Sequelae of SARS CoV 2 Infection

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
IV normal saline (1500mL infusion)
IV normal saline (50mL infusion)
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postural Orthostatic Tachycardia Syndrome focused on measuring POTS, Long COVID, Cognitive

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Patients with diagnosis of Long COVID SARS-COV2 test positive Symptoms > 12 weeks post COVID Subjective complaint of 'brain fog" or cognitive dysfunction Patients with diagnosis of Postural Orthostatic Syndrome (POTS) from the Calgary Autonomic Investigation and Management Clinic Subjective complaint of 'brain fog" or cognitive impairment Healthy participants Without POTS or "brain fog" Age 18 to 60 years Female and Male Able to give an informed consent Exclusion Criteria: Patients with overt causes for POTS (e.g., dehydration, prolonged bed rest) An inability to safely withdraw from medicine(s) that could make test interpretation difficult and impossible. Other factors which are in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule. Unable to give an informed consent.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    1500mL Normal Saline

    50mL Normal Saline

    Arm Description

    1500mL of normal saline infused intravenously.

    50mL of normal saline infused intravenously.

    Outcomes

    Primary Outcome Measures

    5RTI Reaction Time task (Standing)
    5RTI Reaction Time Score (Standing) after 1500mL IV saline compared to 5RTI score after 50mL IV saline measured in milliseconds (ms). The minimum score is 100 ms and the maximum score is 5100 ms. A longer time is a worse outcome.

    Secondary Outcome Measures

    Reaction Time Test (Psychomotor Speed)
    Reaction Time Test score after 1500mL IV saline compared to after 50mL IV saline measured in milliseconds. The minimum score is 100 ms and the maximum score is 5100 ms. A longer time is a worse outcome.
    Paired Associates Learning (Visual Episodic Memory)
    Paired Associates Learning score after 1500mL IV saline compared to after 50mL IV saline measured in arbitrary units. The minimum score is 0 and the maximum score is 70. A higher score is a worse outcome.
    Verbal Recognition Memory (Verbal memory)
    Verbal Recognition Memory test score after 1500mL IV saline compared to after 50mL IV saline. The range is 0-18. A higher score is a better outcome.
    Multitasking Test (Executive Function - Inhibition)
    Multitasking Test Time after 1500mL IV saline compared to after 50mL IV saline measured in ms. The range is 100 - 2000 ms. A longer time is a worse is a worse outcome.

    Full Information

    First Posted
    June 13, 2023
    Last Updated
    October 11, 2023
    Sponsor
    University of Calgary
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05914649
    Brief Title
    NC Testing in LC & POTS
    Official Title
    Neurocognitive Testing in Long COVID and Postural Tachycardia Syndrome Patients With Normal Saline: A Pilot Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    December 31, 2026 (Anticipated)
    Study Completion Date
    December 31, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Calgary

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Patients with Postural Orthostatic Tachycardia Syndrome (POTS) and Post-Acute Sequelae of COVID (PASC, or "Long COVID") experience cognitive dysfunction. The investigators will test the hypothesis that 1500mL of IV saline will improve cognitive function in patients with POTS and Long COVID, compared to placebo (50mL of saline).
    Detailed Description
    Many POTS patients report cognitive dysfunction, otherwise referred to as brain fog, mental fog, mental clouding, or mental fatigue. Importantly, this cognitive dysfunction can occur even while lying down or seated, limiting ability to engage in work and educational activities. Despite the prevalence and clinical impact of cognitive dysfunction in POTS, there are limited studies examining this phenomenon. Many patients with post acute sequelae of SARS- COV-2 (PASC, or "Long COVID") experience symptoms such as subjective cognitive impairment, ("brain fog"), fatigue, memory loss, headache, and fluctuation of blood pressure amongst other signs and symptoms. This study will measure cognitive function in patients with POTS and Long COVID, compared to healthy controls. This study will also evaluate IV normal saline (1500mL infusion) as a potential treatment for reduced cognitive function in POTS and Long COVID. A 50mL saline infusion will be used as a placebo control in this cross-over study. The findings from this study will be an initial first step towards understanding any neurocognitive impairment in participants with long COVID and POTS patients. This is a critical first step to future studies to assess underlying pathophysiology and potential treatments. Primary hypothesis: Some objective measures of neurocognitive functions will improve in Long COVID and POTS patients after the infusion of 1500mL of normal saline compared to 50mL placebo control. The primary analysis will compare the standing 5RTI task on the CANTAB testing scores between 1500mL saline infusion and 50mL saline infusion (placebo). Study Day and Instrumentation: A trained research staff member will insert an intravenous line in the vein of the participant arm to give either 1500 ml or 50 ml of normal saline which can take up to 30 minutes. Normal saline will be administered by a trained research staff member. After instrumentation, participant will lie supine for at least 10 minutes while their ECG & BP are continuously recorded. The participant will stand up quickly (within several seconds), and then stand quietly for about 11 minutes while recording continues. The lying-> stand will allow us to assess for hemodynamics of IST, POTS & OH. Any time during the test, they want to sit down a chair will be provided to them. After the stand test, participant will be asked to do the Trail Making Test (TMT) in the standing position. They will be asked to join numbers and letters in a circle. This test should not take more than approximately 10 minutes. Any time during the test, they want to sit down a chair will be provided to them. The participant will then be seated comfortably in a chair with their feet on the floor. They will be asked to do the Heart Counting Task (HCT) test. The participant will be asked to count their heartbeats without using their hands or other means to feel pulse that might affect their performance. This test will approximately take around 10 minutes. The research team will then de instrument the participant except for the Blood Pressure cuff on the arm. The research team will continue to monitor the blood pressure throughout the study. Neuropsychological testing of the cognitive domains of memory, attention and executive function will be assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) both seated and standing. . The seated cognitive testing period will last approximately 60 minutes. The participant will be asked to stand unaided for up to 30 minutes and repeat portions of the CANTAB tests. Blood Pressure will be monitored throughout the stand test. A chair will be provided to the participant in case they would want to sit down. At the end of each stand test, the investigators will assess patient symptoms using the Vanderbilt Orthostatic Symptoms Score (VOSS). VOSS is a 9-item symptom-rating with each item score from 0-10 (worst) for a total score ranging from 0-90. The study will then be finished. The investigators will remove the recording patches and electrodes. The participant will then be booked for the second visit according to their convenience where all the tests will be repeated, including: IV insertion & infusion of normal saline, supine, stand, and the cognitive tests (CANTAB, TMT & HCT). Repeating these tests will help the research team in assessing if, the cognitive functions will improve for the Long COVID and POTS patients with blood volume expansion with the infusion of normal saline. CANTAB Testing Protocol: CANTAB tests have demonstrated sensitivity to detecting changes in neuropsychological performance and include tests of working memory, learning and executive function; visual, verbal and episodic memory; attention, information processing and reaction time; social and emotion recognition, decision making and response control. The subtests that will be used in this study for seated cognitive function are: Reaction Time Test (psychomotor Speed), Rapid Visual Information processing (Attention), Paired Associates Learning (Visual Episodic Memory), Spatial Span (Working memory), Verbal Recognition Memory (Verbal memory), Multitasking Test (Executive Function - Inhibition), Stocking of Cambridge (Executive Function - Planning) and the Emotional Bias Task (Emotion Processing). All tests are administered using a touch screen tablet, participants will respond to each test on-screen. Standardized written and audio instructions are given to participants through the software, and practice trials are completed before each test, reducing practice effects. Seated testing will be completed in approximately 60 minutes. The Reaction Time Test, Rapid Visual Processing and the Multi Tasking tests will be repeated upon standing and will take approximately 30 minutes to complete. After the in-lab portion of the study, participants will complete a series of validated questionnaires through a paper or RedCap secure web application for assessment of psychiatric symptoms. A unique URL link will be sent to the participants via Redcap Survey. These online surveys will take ~60 minutes to complete.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Postural Orthostatic Tachycardia Syndrome, Post Acute Sequelae of SARS CoV 2 Infection
    Keywords
    POTS, Long COVID, Cognitive

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Model Description
    Participants will complete both the active and placebo arms of the study in a random order.
    Masking
    Participant
    Masking Description
    Participants will be blinded to volume of saline being infused (1500mL or 50mL).
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    1500mL Normal Saline
    Arm Type
    Experimental
    Arm Description
    1500mL of normal saline infused intravenously.
    Arm Title
    50mL Normal Saline
    Arm Type
    Placebo Comparator
    Arm Description
    50mL of normal saline infused intravenously.
    Intervention Type
    Other
    Intervention Name(s)
    IV normal saline (1500mL infusion)
    Intervention Description
    1500mL of IV normal saline will be infused intravenously
    Intervention Type
    Other
    Intervention Name(s)
    IV normal saline (50mL infusion)
    Intervention Description
    50mL of IV normal saline will be infused intravenously as a placebo control.
    Primary Outcome Measure Information:
    Title
    5RTI Reaction Time task (Standing)
    Description
    5RTI Reaction Time Score (Standing) after 1500mL IV saline compared to 5RTI score after 50mL IV saline measured in milliseconds (ms). The minimum score is 100 ms and the maximum score is 5100 ms. A longer time is a worse outcome.
    Time Frame
    During Procedure (3 hours)
    Secondary Outcome Measure Information:
    Title
    Reaction Time Test (Psychomotor Speed)
    Description
    Reaction Time Test score after 1500mL IV saline compared to after 50mL IV saline measured in milliseconds. The minimum score is 100 ms and the maximum score is 5100 ms. A longer time is a worse outcome.
    Time Frame
    During Procedure (3 hours)
    Title
    Paired Associates Learning (Visual Episodic Memory)
    Description
    Paired Associates Learning score after 1500mL IV saline compared to after 50mL IV saline measured in arbitrary units. The minimum score is 0 and the maximum score is 70. A higher score is a worse outcome.
    Time Frame
    During Procedure (3 hours)
    Title
    Verbal Recognition Memory (Verbal memory)
    Description
    Verbal Recognition Memory test score after 1500mL IV saline compared to after 50mL IV saline. The range is 0-18. A higher score is a better outcome.
    Time Frame
    During Procedure (3 hours)
    Title
    Multitasking Test (Executive Function - Inhibition)
    Description
    Multitasking Test Time after 1500mL IV saline compared to after 50mL IV saline measured in ms. The range is 100 - 2000 ms. A longer time is a worse is a worse outcome.
    Time Frame
    During Procedure (3 hours)
    Other Pre-specified Outcome Measures:
    Title
    Sitting heart rate
    Description
    Sitting heart rate after 1500mL IV saline compared to after 50mL IV saline.
    Time Frame
    During Procedure (10 minutes)
    Title
    Standing heart rate
    Description
    Standing heart rate after 1500mL IV saline compared to after 50mL IV saline.
    Time Frame
    During Procedure (10 minutes)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Patients with diagnosis of Long COVID SARS-COV2 test positive Symptoms > 12 weeks post COVID Subjective complaint of 'brain fog" or cognitive dysfunction Patients with diagnosis of Postural Orthostatic Syndrome (POTS) from the Calgary Autonomic Investigation and Management Clinic Subjective complaint of 'brain fog" or cognitive impairment Healthy participants Without POTS or "brain fog" Age 18 to 60 years Female and Male Able to give an informed consent Exclusion Criteria: Patients with overt causes for POTS (e.g., dehydration, prolonged bed rest) An inability to safely withdraw from medicine(s) that could make test interpretation difficult and impossible. Other factors which are in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule. Unable to give an informed consent.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Satish R Raj, MD MSCI
    Phone
    4032106152
    Email
    autonomic.research@ucalgary.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Tanya Siddiqui, MBBS
    Email
    autonomic.research@ucalgary.ca

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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