An interventional study of Non-invasive vagus nerve stimulation and Sham Intervention in Post-COVID-19 Syndrome, Postural Tachycardia Syndrome and Dysautonomia, sponsored by Icahn School of Medicine at Mount Sinai. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-08.
Sponsored by Icahn School of Medicine at Mount Sinai · Not applicable, Interventional, and Treatment
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.
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 40 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Icahn School of Medicine at Mount Sinai is the lead sponsor of 764 studies on the registry; 181 are open to participants now.
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Clinical diagnosis of dysautonomia following an acute COVID-19 infection at least 3 months prior. See below for criteria:
Exclusion Criteria:
Pregnant persons will not be included in this study for the following reasons:
According to the device manufacturer, the following contraindications will be followed during the screening process:
Participants in the Non-Invasive Vagus Nerve Stimulation arm will have devices calibrated to a therapeutic setting.
Device: Non-invasive vagus nerve stimulation
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.
Device: Non-invasive vagus nerve stimulation · Device: Sham Intervention
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.
Also known as: Vagus nerve stimulation
Participants will take a placebo device home for 6 weeks and use daily.
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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.
Time frame: Baseline (Week 0)
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.
Time frame: Week 2
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.
Time frame: Week 5
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.
Time frame: Week 8
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.
Time frame: Week 12
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Icahn School of Medicine at Mount Sinai