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Long COVID Immune Profiling

Primary Purpose

Long COVID, POTS - Postural Orthostatic Tachycardia Syndrome, Autonomic Dysfunction

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
IL-6
cytokines (IL-17, and IFN-ɣ)
Compass 31
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Long COVID focused on measuring SARS-CoV-2 infection, POTS, Orthostatic Intolerance, Long COVID, Long hauler COVID infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Subjects will be 18 years or older, men and women. History of confirmed COVID-19 infection (positive contact and symptoms, antigen test or PCR). POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms. Post-COVID-19 POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms. Symptoms occurred within 2 months after COVID infection and persistent until enrollment in the study. Exclusion Criteria: Individuals with a history of physician diagnosed myocardial infarction, angina, heart failure, stroke, or transient ischemic attack, or who had undergone an invasive procedure for CVD (coronary artery bypass graft, angioplasty, valve replacement, pacemaker placement or other vascular surgeries). Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study. Chronic use of steroids, anti-IL6 (omalizumab), anti-TNF-alpha, other immunosuppressants. Chronic use of NSAID. Should not enroll if taking without one week prior to blood sampling. Treatment with plasmapheresis, IVIG or other immune modulator

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Other

    Other

    Other

    Arm Label

    Post- COVID 19 POTS patients

    POTS patients

    Post- COVID 19 POTS patients with Controls

    Arm Description

    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31): In post-COVID-19 POTS (cases).

    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: patients with diagnosis of POTS

    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: Controls are :COVID-19 infected without sequelae

    Outcomes

    Primary Outcome Measures

    IL-6 levels
    Parasympathetic (PNS) function, protects against inflammation. To Evaluate level of inflammation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity. The primary endpoint is IL-6 levels

    Secondary Outcome Measures

    Orthostatic Symptoms Score
    Standardized Orthostatic Symptoms Score COMPASS-31: Composite Autonomic Symptom Score The COMPASS-31 is a widely-utilized patient questionnaire that provides a quantitative assessment of the severity and distribution of autonomic symptoms . This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function.
    cytokines (IL-17, and IFN-ɣ)
    Proinflammatory cells and its secreted cytokines (IL-17, and IFN-ɣ) in Post-COVID-19 POTS patients, comparing to controls

    Full Information

    First Posted
    August 31, 2023
    Last Updated
    September 6, 2023
    Sponsor
    Vanderbilt University Medical Center
    Collaborators
    American Heart Association
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06027255
    Brief Title
    Long COVID Immune Profiling
    Official Title
    Long COVID Immune Profiling
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    October 31, 2025 (Anticipated)
    Study Completion Date
    October 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Vanderbilt University Medical Center
    Collaborators
    American Heart Association

    4. Oversight

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

    5. Study Description

    Brief Summary
    Parasympathetic nervous system (PNS) is part of the body's autonomic nervous system(PNS) protects body against inflammation. Study shows that reduced PNS function activity is associated with persistent inflammation. Preliminary data from the studies shows, that post-COVID-19 POTS patients have reduced parasympathetic (PNS) function. Given that the PNS protects against inflammation, this clinical trial aims to prove that post-COVID-19 POTS is caused by reduced PNS activity, which in turn, contributes to persistent inflammation, orthostatic intolerance, and OI symptoms. The study will evaluate immune cell activation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity.
    Detailed Description
    COVID-19 infections can cause a disabling syndrome that persists beyond the 3-month convalescence period. The term post-acute COVID-19 syndrome or Long COVID is coined to describe a cluster of symptoms consisting of fatigue, chest pain, reduced exercise tolerance, tachycardia, and cognitive impairment. Persistent tachycardia remains one of the most common complaints, reported in 9% of patients at 6 months post-infection. These symptoms overlap with those present in patients with Postural orthostatic tachycardia syndrome (POTS). It is noteworthy that about half of POTS patients also report a history of viral infection prior to the development of these symptoms. Post-COVID-19 tachycardia syndrome, POTS variant: It present with chronic tachycardia with symptoms of orthostatic intolerance (OI) without any other identifiable cause. In addition, non-specific symptoms such as fatigue, headache, and "brain fog", commonly described in POTS patients are also present in this novel condition. Elevated levels of inflammatory markers CRP,D-dimer and IL-6 are found in Long COVID patients. Data in POTS, which resembles post-COVID tachycardia syndrome, shows increased cytokines including IL-6, IL-1b, and TNF-a. Notably, stimulation of the efferent vagus nerve (PNS), has been shown to reduce proinflammatory markers production and systemic inflammation. Hence, decreased PNS function, as reported with acute SARS-CoV-2 infection and in post-COVID-19 POTS patients, may render these patients prone to persistent inflammation. To determine the link between PNS activity and immune activation in post-COVID-19 POTS, the study aims to evaluate immune cell activation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity. Rationale and Specific Aims: Preliminary data shows that post-COVID-19 POTS patients have reduced parasympathetic (PNS) function. Given that the PNS protects against inflammation, we hypothesize that post-COVID-19 POTS is caused by reduced PNS activity, which in turn, contributes to persistent inflammation, orthostatic intolerance, and OI symptoms. Primary Aim: Test the hypothesis that reduced PNS activity is associated with persistent inflammation in patients with post-COVID-19 POTS. Study Participants: This is a cross-sectional study conducted, up to 150 patients will be enrolled, 50 POTS without Long-COVID, 50 POTS with Long-COVID and 50 controls with history of COVID-19 infection without sequelae. Study Procedures Recruitment: Subjects will be recruited from referrals to the Vanderbilt Autonomic Dysfunction Center (ADC) Study visit: Assessments: Autonomic symptoms assessment questionnaire (COMPASS-31) Quality of life EQ-5D PROMIS scale (Functional Activities Questionnaire in Older Adults with Dementia), OHQ (Orthostatic Hypotension Questionnaire) CBS (Cambridge Brain sciences: Web based cognitive assessment platform, Optional), and neuropsychological tests Blood sample collection: CBC, CMP, C-reactive protein (CRP), D-dimer, Flow cytometry study, PBMC isolation Autonomic function tests: Testing performed at Vanderbilt ADC within 10 years of the study visit will be utilized. Testing will not be repeated solely for the purposes of this study. Statistical Considerations Biostatistical Section The primary endpoint serum IL-6. The proposed sample size of 150 (50 POTD, 50 Long COVID POTS patients and 50 controls) provides more than 90% power to detect an effect size of 0.62 for the mean difference in IL-6 between post-COVID-19 POTS (cases) and controls (COVID-19 infected w/o sequelae), with the two-sided type I error = 5%. This calculation is based on the preliminary data of mean difference of IL-6 ≈ 1.82 and the SD ≈ 2.94 in POTS.16 The effect size is defined as the ratio of mean IL-6 difference between cases and controls to standard deviation. Data analysis plan: Demographic information will be tabulated. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percent and frequencies for categorical parameters, will be presented. T-test or Mann-Whitney (as appropriate) will be applied to examine the mean differences between cases and control with respect to the outcomes. The conditional logistic regression model will be applied for the multivariable data analysis. The adjusted p-values and the adjusted 95% confidence intervals (CIs) will be reported.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Long COVID, POTS - Postural Orthostatic Tachycardia Syndrome, Autonomic Dysfunction
    Keywords
    SARS-CoV-2 infection, POTS, Orthostatic Intolerance, Long COVID, Long hauler COVID infection

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    To enroll up to 150 patients, 50 POTS without Long-COVID, 50 POTS with Long-COVID and 50 controls with history of COVID-19 infection without sequelae
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    150 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Post- COVID 19 POTS patients
    Arm Type
    Other
    Arm Description
    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31): In post-COVID-19 POTS (cases).
    Arm Title
    POTS patients
    Arm Type
    Other
    Arm Description
    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: patients with diagnosis of POTS
    Arm Title
    Post- COVID 19 POTS patients with Controls
    Arm Type
    Other
    Arm Description
    Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: Controls are :COVID-19 infected without sequelae
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    IL-6
    Intervention Description
    Compare IL-6 level , as a marker of inflammation in all the 3 groups: POTS patients post-COVID-19 POTS gender, age, and BMI-matched controls, with history of COVID-19 infection without sequelae.
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    cytokines (IL-17, and IFN-ɣ)
    Intervention Description
    Compare Proinflammatory cells and its secreted cytokines (IL-17, and IFN-ɣ) in all the 3 groups: POTS patients post-COVID-19 POTS gender, age, and BMI-matched controls, with history of COVID-19 infection without sequelae
    Intervention Type
    Behavioral
    Intervention Name(s)
    Compass 31
    Intervention Description
    Autonomic symptoms assessment questionnaire (COMPASS 31), in post-COVID-19 POTS and compare with POTS patients
    Primary Outcome Measure Information:
    Title
    IL-6 levels
    Description
    Parasympathetic (PNS) function, protects against inflammation. To Evaluate level of inflammation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity. The primary endpoint is IL-6 levels
    Time Frame
    Baseline
    Secondary Outcome Measure Information:
    Title
    Orthostatic Symptoms Score
    Description
    Standardized Orthostatic Symptoms Score COMPASS-31: Composite Autonomic Symptom Score The COMPASS-31 is a widely-utilized patient questionnaire that provides a quantitative assessment of the severity and distribution of autonomic symptoms . This questionnaire generates a weighted score from 0 to 100, and questions fall into one of six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor function.
    Time Frame
    Baseline
    Title
    cytokines (IL-17, and IFN-ɣ)
    Description
    Proinflammatory cells and its secreted cytokines (IL-17, and IFN-ɣ) in Post-COVID-19 POTS patients, comparing to controls
    Time Frame
    Baseline

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Subjects will be 18 years or older, men and women. History of confirmed COVID-19 infection (positive contact and symptoms, antigen test or PCR). POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms. Post-COVID-19 POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms. Symptoms occurred within 2 months after COVID infection and persistent until enrollment in the study. Exclusion Criteria: Individuals with a history of physician diagnosed myocardial infarction, angina, heart failure, stroke, or transient ischemic attack, or who had undergone an invasive procedure for CVD (coronary artery bypass graft, angioplasty, valve replacement, pacemaker placement or other vascular surgeries). Inability to comply with the protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study. Chronic use of steroids, anti-IL6 (omalizumab), anti-TNF-alpha, other immunosuppressants. Chronic use of NSAID. Should not enroll if taking without one week prior to blood sampling. Treatment with plasmapheresis, IVIG or other immune modulator

    12. IPD Sharing Statement

    Learn more about this trial

    Long COVID Immune Profiling

    We'll reach out to this number within 24 hrs