Back to resultsVNS for Long-COVID-19
Primary Purpose
Post-COVID-19 Syndrome, Postural Tachycardia Syndrome, Dysautonomia
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Non-invasive vagus nerve stimulation
Sham Intervention
Sponsored by
About this trial
This is an interventional treatment trial for Post-COVID-19 Syndrome
Eligibility Criteria
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study At least 18 years of age Clinical diagnosis of dysautonomia following an acute COVID-19 infection at least 3 months prior. See below for criteria: clinical diagnosis of autonomic dysfunction as evaluated by a qualified healthcare provider 2 or more if the following clinical assessment findings symptomatic exacerbation during active stand test tachycardia on active stand test tachycardia on orthostatic vitals assessment hypotension on orthostatic vitals assessment hypertension in orthostatic vitals assessment symptom exacerbation on orthostatic vitals assessment English speaking Exclusion Criteria: • Pregnancy or lactation: Pregnant persons will not be included in this study for the following reasons: There is not sufficient data surrounding the hormone cycle changes during pregnancy and its effects on the condition being studied (PCD). The results could be skewed due to pregnancy. Of note, there are no risks for pregnant persons to participate. According to the device manufacturer, the following contraindications will be followed during the screening process: Patients with an active implantable medical device, such as a cardiac pacemaker, heading aid implant, or any implanted metallic or electronic device Patients with a history of baseline cardiac disease or atherosclerotic cardiovascular disease, including congestive heath failure (CHF), known severe coronary artery disease or recent myocardial infarction (within 5 years) Patients with diagnosed bradycardia Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy) Patients diagnosed with narrowing of the arteries (carotid atherosclerosis) Patients whose pain syndromes are undiagnosed Pediatric patients Pregnant women
Sites / Locations
- Abilities Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Non-invasive Vagus Nerve Stimulation
Sham Vagus Nerve Stimulation
Arm Description
Participants in the Non-Invasive Vagus Nerve Stimulation arm will have devices calibrated to a therapeutic setting.
Participants in the "sham VNS" arm will be asked to use the VNS device daily on a sham setting for six weeks and will be given the opportunity to "crossover" into the active VNS arm once they have completed the sham arm.
Outcomes
Primary Outcome Measures
Composite Dysautonomia Symptom Score (COMPASS 31)
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Composite Dysautonomia Symptom Score (COMPASS 31)
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Composite Dysautonomia Symptom Score (COMPASS 31)
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Composite Dysautonomia Symptom Score (COMPASS 31)
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Composite Dysautonomia Symptom Score (COMPASS 31)
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Secondary Outcome Measures
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Neuro Quality of Life Score
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Neuro Quality of Life Score
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Neuro Quality of Life Score
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Neuro Quality of Life Score
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Neuro Quality of Life Score
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Medical Research Council (MRC) Dyspnoea Scale
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Medical Research Council (MRC) Dyspnoea Scale
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Medical Research Council (MRC) Dyspnoea Scale
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Medical Research Council (MRC) Dyspnoea Scale
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Medical Research Council (MRC) Dyspnoea Scale
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Post-Exertional Malaise (PEM) Screener
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Post-Exertional Malaise (PEM) Screener
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Post-Exertional Malaise (PEM) Screener
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Post-Exertional Malaise (PEM) Screener
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Post-Exertional Malaise (PEM) Screener
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Total score ranges 0-40, with higher scores indicate worse health outcomes.
EQ-5D-5L Quality of Life Score
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
EQ-5D-5L Quality of Life Score
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
EQ-5D-5L Quality of Life Score
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
EQ-5D-5L Quality of Life Score
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
EQ-5D-5L Quality of Life Score
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Plasma IL-6 levels
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-6 levels
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body in different ways.
Plasma IL-6 levels
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-6 levels
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-6 levels
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-1 levels
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-1 levels
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-1 levels
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-1 levels
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-1 levels
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-10 levels
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-10 levels
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-10 levels
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-10 levels
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma IL-10 levels
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma HS-CRP levels
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma HS-CRP levels
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma HS-CRP levels
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma HS-CRP levels
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Plasma HS-CRP levels
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Morning salivary cortisol levels
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Morning salivary cortisol levels
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Morning salivary cortisol levels
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Morning salivary cortisol levels
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Morning salivary cortisol levels
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
End-tidal CO2 levels
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
End-tidal CO2 levels
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
End-tidal CO2 levels
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
End-tidal CO2 levels
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
End-tidal CO2 levels
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Full Information
NCT ID
NCT05630040
First Posted
November 21, 2022
Last Updated
June 22, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
1. Study Identification
Unique Protocol Identification Number
NCT05630040
Brief Title
VNS for Long-COVID-19
Official Title
Vagus Nerve Simulation for Long-COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 11, 2022 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
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
The goal of this proposed clinical case series is to evaluate the effect of a non-invasive vagus nerve stimulation paradigm on: 1) Symptom reporting via validated patient reported outcomes, and 2) objective clinical biomarkers of autonomic nervous system function.
This will be a placebo controlled, randomized controlled trial with a crossover design built in. This study will aim to recruit 40 people with Long COVID to be a part of this research.
Detailed Description
Participants will be randomized into one of two arms. Those in the "active VNS" arm will be sent home with a portable VNS device and asked to perform a daily VNS protocol designed to down regulate sympathetic nervous system activity for six weeks.
Those in the "sham VNS" arm will be asked to use the VNS device daily on a sham setting for six weeks. Those randomized to the sham group will be given the opportunity to "crossover" into the active VNS arm once they have completed the sham arm (Week 12). The participant and assessor will be blinded.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-COVID-19 Syndrome, Postural Tachycardia Syndrome, Dysautonomia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
This will be a placebo controlled, double blind, randomized control trial with a crossover design built in.
Those randomized to the sham group will be given the opportunity to "crossover" into the active VNS arm once they have completed the sham arm (Week 12).
Masking
ParticipantOutcomes Assessor
Masking Description
This study will have a blinded assessor and all participants will be blinded.
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Non-invasive Vagus Nerve Stimulation
Arm Type
Experimental
Arm Description
Participants in the Non-Invasive Vagus Nerve Stimulation arm will have devices calibrated to a therapeutic setting.
Arm Title
Sham Vagus Nerve Stimulation
Arm Type
Sham Comparator
Arm Description
Participants in the "sham VNS" arm will be asked to use the VNS device daily on a sham setting for six weeks and will be given the opportunity to "crossover" into the active VNS arm once they have completed the sham arm.
Intervention Type
Device
Intervention Name(s)
Non-invasive vagus nerve stimulation
Other Intervention Name(s)
Vagus nerve stimulation
Intervention Description
Participants will take the VNS device home and asked to perform a daily VNS protocol designed to down regulate sympathetic nervous system activity for 6 weeks.
Intervention Type
Device
Intervention Name(s)
Sham Intervention
Intervention Description
Participants will take a placebo device home for 6 weeks and use daily.
Primary Outcome Measure Information:
Title
Composite Dysautonomia Symptom Score (COMPASS 31)
Description
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Time Frame
Baseline (Week 0)
Title
Composite Dysautonomia Symptom Score (COMPASS 31)
Description
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Time Frame
Week 2
Title
Composite Dysautonomia Symptom Score (COMPASS 31)
Description
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Time Frame
Week 5
Title
Composite Dysautonomia Symptom Score (COMPASS 31)
Description
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Time Frame
Week 8
Title
Composite Dysautonomia Symptom Score (COMPASS 31)
Description
COMPASS-31 (the composite autonomic symptom) score is a self-rating questionnaire evaluating six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains.
The total score will be between 0 to 100, and a higher score indicates more severe autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, is internally consistent and applies a much-simplified scoring algorithm suitable for widespread use in autonomic research and practice.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Fatigue Severity Scale (FSS)
Description
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Time Frame
Baseline (Week 0)
Title
Fatigue Severity Scale (FSS)
Description
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Time Frame
Week 2
Title
Fatigue Severity Scale (FSS)
Description
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Time Frame
Week 5
Title
Fatigue Severity Scale (FSS)
Description
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Time Frame
Week 8
Title
Fatigue Severity Scale (FSS)
Description
The Fatigue Severity Scale measures fatigue severity. The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue.
Time Frame
Week 12
Title
Neuro Quality of Life Score
Description
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Time Frame
Baseline (Week 0)
Title
Neuro Quality of Life Score
Description
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Time Frame
Week 2
Title
Neuro Quality of Life Score
Description
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Time Frame
Week 5
Title
Neuro Quality of Life Score
Description
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Time Frame
Week 8
Title
Neuro Quality of Life Score
Description
The NeuroQOL is a self-report of health-related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five-option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.
Time Frame
Week 12
Title
Medical Research Council (MRC) Dyspnoea Scale
Description
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Time Frame
Baseline (Week 0)
Title
Medical Research Council (MRC) Dyspnoea Scale
Description
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Time Frame
Week 2
Title
Medical Research Council (MRC) Dyspnoea Scale
Description
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Time Frame
Week 5
Title
Medical Research Council (MRC) Dyspnoea Scale
Description
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Time Frame
Week 8
Title
Medical Research Council (MRC) Dyspnoea Scale
Description
The MRC breathlessness scale comprises five statements that describe almost the entire range of respiratory disability from none (Grade 1) to almost complete incapacity (Grade 5). Full scale from 1-5, with higher score indicating more severe symptoms.
Time Frame
Week 12
Title
Post-Exertional Malaise (PEM) Screener
Description
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Time Frame
Baseline (Week 0)
Title
Post-Exertional Malaise (PEM) Screener
Description
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Time Frame
Week 2
Title
Post-Exertional Malaise (PEM) Screener
Description
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Time Frame
Week 5
Title
Post-Exertional Malaise (PEM) Screener
Description
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Higher scores indicate worse health outcomes. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Time Frame
Week 8
Title
Post-Exertional Malaise (PEM) Screener
Description
Post-exertional malaise (PEM) is the worsening of symptoms following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. The PEM assesses symptom frequency and severity over a 6-month look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Total score ranges 0-40, with higher scores indicate worse health outcomes.
Time Frame
Week 12
Title
EQ-5D-5L Quality of Life Score
Description
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Time Frame
Baseline (Week 0)
Title
EQ-5D-5L Quality of Life Score
Description
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Time Frame
Week 2
Title
EQ-5D-5L Quality of Life Score
Description
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Time Frame
Week 5
Title
EQ-5D-5L Quality of Life Score
Description
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Time Frame
Week 8
Title
EQ-5D-5L Quality of Life Score
Description
The EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state, thus, higher scores indicate better health outcomes.
Time Frame
Week 12
Title
Plasma IL-6 levels
Description
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Baseline (Week 0)
Title
Plasma IL-6 levels
Description
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body in different ways.
Time Frame
Week 2
Title
Plasma IL-6 levels
Description
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 5
Title
Plasma IL-6 levels
Description
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 8
Title
Plasma IL-6 levels
Description
Plasma IL-6 levels as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 12
Title
Plasma IL-1 levels
Description
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Baseline (Week 0)
Title
Plasma IL-1 levels
Description
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 2
Title
Plasma IL-1 levels
Description
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 5
Title
Plasma IL-1 levels
Description
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 8
Title
Plasma IL-1 levels
Description
Plasma IL-1 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 12
Title
Plasma IL-10 levels
Description
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Baseline (Week 0)
Title
Plasma IL-10 levels
Description
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 2
Title
Plasma IL-10 levels
Description
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 5
Title
Plasma IL-10 levels
Description
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 8
Title
Plasma IL-10 levels
Description
Plasma IL-10 levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 12
Title
Plasma HS-CRP levels
Description
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Baseline (Week 0)
Title
Plasma HS-CRP levels
Description
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 2
Title
Plasma HS-CRP levels
Description
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 5
Title
Plasma HS-CRP levels
Description
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 8
Title
Plasma HS-CRP levels
Description
Plasma HS-CRP levels: as a metric of sympathetic nervous system activation. Plasma testing evaluates for evidence of inflammation in the body.
Time Frame
Week 12
Title
Morning salivary cortisol levels
Description
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Time Frame
Baseline (Week 0)
Title
Morning salivary cortisol levels
Description
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Time Frame
Week 2
Title
Morning salivary cortisol levels
Description
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Time Frame
Week 5
Title
Morning salivary cortisol levels
Description
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Time Frame
Week 8
Title
Morning salivary cortisol levels
Description
Morning salivary cortisol levels: As a metric of sympathetic nervous system activation. Morning salivary cortisol levels evaluate changes in the body's waking hormone responses, which indicate changes in nervous system activation in response to the intervention.
Time Frame
Week 12
Title
End-tidal CO2 levels
Description
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Time Frame
Baseline (Week 0)
Title
End-tidal CO2 levels
Description
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Time Frame
Week 2
Title
End-tidal CO2 levels
Description
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Time Frame
Week 5
Title
End-tidal CO2 levels
Description
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Time Frame
Week 8
Title
End-tidal CO2 levels
Description
End-tidal CO2 levels: As a metric of sympathetic nervous system activation measured using a capnograph. Patients with post-COVID dysautonomia will be hypocapnic (low end-tidal CO2). High or low levels of end-tidal CO2 can drive symptoms in patients.
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
At least 18 years of age
Clinical diagnosis of dysautonomia following an acute COVID-19 infection at least 3 months prior. See below for criteria:
clinical diagnosis of autonomic dysfunction as evaluated by a qualified healthcare provider
2 or more if the following clinical assessment findings
symptomatic exacerbation during active stand test
tachycardia on active stand test
tachycardia on orthostatic vitals assessment
hypotension on orthostatic vitals assessment
hypertension in orthostatic vitals assessment
symptom exacerbation on orthostatic vitals assessment
English speaking
Exclusion Criteria:
• Pregnancy or lactation:
Pregnant persons will not be included in this study for the following reasons:
There is not sufficient data surrounding the hormone cycle changes during pregnancy and its effects on the condition being studied (PCD). The results could be skewed due to pregnancy.
Of note, there are no risks for pregnant persons to participate.
According to the device manufacturer, the following contraindications will be followed during the screening process:
Patients with an active implantable medical device, such as a cardiac pacemaker, heading aid implant, or any implanted metallic or electronic device
Patients with a history of baseline cardiac disease or atherosclerotic cardiovascular disease, including congestive heath failure (CHF), known severe coronary artery disease or recent myocardial infarction (within 5 years)
Patients with diagnosed bradycardia
Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy) Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
Patients whose pain syndromes are undiagnosed
Pediatric patients
Pregnant women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Putrino, PT, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abilities Research Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will not be shared.
Learn more about this trial
VNS for Long-COVID-19
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