VNS for Long-COVID-19

Post-COVID-19 Syndrome Clinical Trial

Official title:

Vagus Nerve Simulation for Long-COVID-19

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05630040
• Other study ID #: STUDY-22-00985
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 11, 2022
• Est. completion date: June 2024

Study information

• Verified date: March 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• COVID-19
• Dysautonomia
• Post-COVID-19 Syndrome
• Postural Orthostatic Tachycardia Syndrome
• Postural Tachycardia Syndrome
• Primary Dysautonomias
• Syndrome
• Tachycardia

Intervention

Device:
• Non-invasive vagus nerve stimulation
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.
• Sham Intervention
Participants will take a placebo device home for 6 weeks and use daily.

Locations

Country	Name	City	State
United States	Abilities Research Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (Week 0)
Primary	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.	Week 2
Primary	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.	Week 5
Primary	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.	Week 8
Primary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	Medical Research Council (MRC) Dyspnoea Scale	The MRC breathlessness scale comprises ?ve 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.	Baseline (Week 0)
Secondary	Medical Research Council (MRC) Dyspnoea Scale	The MRC breathlessness scale comprises ?ve 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.	Week 2
Secondary	Medical Research Council (MRC) Dyspnoea Scale	The MRC breathlessness scale comprises ?ve 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.	Week 5
Secondary	Medical Research Council (MRC) Dyspnoea Scale	The MRC breathlessness scale comprises ?ve 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.	Week 8
Secondary	Medical Research Council (MRC) Dyspnoea Scale	The MRC breathlessness scale comprises ?ve 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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12
Secondary	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.	Baseline (Week 0)
Secondary	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.	Week 2
Secondary	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.	Week 5
Secondary	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.	Week 8
Secondary	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.	Week 12