Mechanisms of Post COVID-19 Tachycardia Syndrome

Overseen By Meena Vinayagam, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Steroids, NSAIDs, Biologics

Disqualifiers: Heart disease, Stroke, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for post-COVID-19 tachycardia syndrome, where individuals experience rapid heartbeats and symptoms like dizziness and brain fog months after recovering from COVID-19. Researchers are testing whether stimulating the vagus nerve in the neck can manage these symptoms and reduce inflammation. The trial includes two groups: one receiving active treatment and the other serving as a comparison to measure inflammation levels. Individuals who have had COVID-19 and now face heart rate issues when standing might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for post-COVID-19 symptoms.

Will I have to stop taking my current medications?

The trial requires that participants do not use certain medications, such as chronic steroids, NSAIDs (non-steroidal anti-inflammatory drugs), and biologics like anti-IL6 and anti-TNF-alpha drugs. If you are taking these, you may need to stop before joining the trial.

What prior data suggests that these methods are safe for assessing post-COVID-19 tachycardia syndrome?

Research shows that using a device on the skin to stimulate the vagus nerve, known as transcutaneous vagus nerve stimulation (tVNS), may help manage symptoms in people with post-COVID-19 POTS. POTS causes a rapid heartbeat when standing up. This treatment aims to help the body's automatic systems, like heart rate, function more smoothly.

Studies have found that tVNS is generally safe. Research on similar conditions reported no major side effects. However, more research with larger groups is needed. While tVNS appears promising, scientists continue to study it to ensure its effectiveness and safety for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it dives into the mystery of post-COVID-19 tachycardia syndrome, especially POTS (Postural Orthostatic Tachycardia Syndrome). While current treatments for POTS often focus on medications that manage heart rate and blood pressure, this study explores something different: the role of inflammation and the autonomic nervous system. One key feature is the use of chronic transcutaneous vagus nerve stimulation (tVNS), a technique that could help restore parasympathetic nervous system function and reduce inflammation. Additionally, the trial examines inflammatory markers like IL-6, which could offer new insights into the biological changes occurring in post-COVID POTS patients. By understanding these mechanisms, researchers hope to uncover more effective ways to manage symptoms and improve quality of life for those affected.

What evidence suggests that this trial's treatments could be effective for post-COVID-19 tachycardia syndrome?

Research has shown that transcutaneous vagus nerve stimulation (tVNS), a treatment participants in this trial may receive, might help individuals with post-COVID-19 POTS. This condition causes an increased heart rate upon standing. Studies suggest that tVNS can help balance the nervous system, which controls heart rate and other automatic functions. By improving nerve function, this treatment might reduce symptoms like a fast heartbeat and fatigue. Early research also indicates that tVNS can lower inflammation, potentially a factor in post-COVID-19 POTS. Overall, these findings suggest tVNS could be a promising way to manage this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Cyndya A Shibao, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals who previously had COVID-19 and now suffer from a condition called post-COVID-19 POTS, characterized by rapid heartbeat when standing up and symptoms like dizziness lasting over 3 months. It's not for those with heart disease, on certain medications like steroids or biologics, post-menopausal women, pregnant or breastfeeding people, those with liver issues, seizure history, recent cardiovascular procedures, substance abuse problems, severe mental conditions, stroke history or impaired kidney function.

Inclusion Criteria

You have previously tested positive for COVID-19 using a specific test called RT-PCR.

I have had a fast heart rate and near-fainting for over 3 months after COVID-19.

I have had a fast heart rate and near-fainting for over 3 months after COVID-19.

Exclusion Criteria

I have had seizures in the past.

I have diabetes (Type 1 or Type 2).

I am currently taking medications like omalizumab or anti-TNF-alpha drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive chronic transcutaneous vagus nerve stimulation (tVNS) for 28 days

4 weeks

3 visits (in-person), 1 visit (telemedicine)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Autonomic Symptoms assessment
• Determine the inflammatory and immune profile of post-COVID-19 POTS patients
• Measurement of PNS activity by HRV (Heart rate Variation)

Trial Overview The study investigates the role of inflammation in long-term rapid heartbeat after COVID-19 (post-COVID-19 POTS). Researchers are measuring levels of an inflammatory marker (IL-6) and examining the effects of chronic stimulation of the parasympathetic nervous system to reduce inflammation in affected patients compared to healthy controls.

How Is the Trial Designed?

Group I: Effect of OI symptoms & inflmmation after Restoring PNS functions in post-COVID POTS patients. Experimental Treatment 1 Intervention

Effects of restoring PNS function in post-COVID-19 POTS patients with chronic transcutaneous vagus nerve stimulation (tVNS) on inflammation, orthostatic tachycardia and OI symptoms.The subjects with POTS will be randomized, where TENS 7000 device will be placed to active and sham location.Autonomic symptoms assessment questionnaire (COMPASS-31),32 quality of life EQ-5D and neuropsychological tests

Group II: Compare inflammatory markers (IL-6) in post- COVID 19 POTS patients with Controls Experimental Treatment 2 Interventions

Biochemical endpoints: Measurement of Inflammatory markers (especially IL-6) in both Post- COVID-19 POTS patients and compare it with controls. Controls are the participants who recovered from COVID 19 infection with no sequelae

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

A study of 14 patients revealed that some individuals who had COVID-19 developed postural tachycardia syndrome (PoTS), showing symptoms similar to those seen in non-COVID-related PoTS cases.

The authors suggest using an active stand test for patients with cardiovascular symptoms after COVID-19 and recommend training for clinicians to manage the expected rise in PoTS cases linked to the pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational case series of postural tachycardia syndrome (PoTS) in post-COVID-19 patients. Gall, NP., James, S., Kavi, L.[2022]

Patients with Post-COVID-19 syndrome (PCS) exhibited significant autonomic dysfunction characterized by increased heart rate and reduced heart rate variability (HRV) parameters, indicating a sympathetic predominance compared to control subjects.

After 6 months, PCS patients showed improvements in HRV and arterial pressure variability, suggesting that the negative effects of COVID-19 on autonomic control may diminish over time, as their responses during the head-up tilt test became similar to those of healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating autonomic nervous system dysfunction among patients with post-COVID condition and prolonged cardiovascular symptoms. da Silva, FS., Bonifácio, LP., Bellissimo-Rodrigues, F., et al.[2023]

A retrospective study found that many patients with post-acute sequelae of SARS-CoV-2 syndrome (PASC) exhibit abnormal autonomic function, similar to patients with postural orthostatic tachycardia syndrome (POTS).

The clinical features of PASC patients were found to be indistinguishable from those of POTS patients, suggesting that dysautonomia may play a significant role in the symptoms experienced by PASC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC). Chung, TH., Azar, A.[2023]

Postural orthostatic tachycardia syndrome (POTS) can develop in 2%-14% of COVID-19 survivors, with many experiencing symptoms like tachycardia and fatigue for up to 6-8 months after infection, indicating a significant long-term impact of COVID-19 on autonomic function.

Management of post-COVID-19 POTS may involve lifestyle changes and medications such as ivabradine or β-blockers, highlighting the need for a multidisciplinary approach to care, as well as further research to understand its mechanisms and improve treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome as a sequela of COVID-19. Ormiston, CK., Świątkiewicz, I., Taub, PR.[2023]

The study analyzed heart rate variability (HRV) in 74 participants, including 37 COVID-19 survivors and 37 healthy controls, revealing significant differences in HRV measures after a 6-minute walk test, indicating that COVID-19 may impact cardiac autonomic function even after recovery.

HRV analysis during recovery from COVID-19 can be a valuable tool for monitoring cardiovascular health, suggesting that exercise impacts heart function and recovery in survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiac Comeback-Beating Stronger: Exploring the Remarkable Resilience of the Heart in COVID-19 Recovery through Cardiac Autonomic Analysis. Garg, S., Saini, P., Rizvi, MR., et al.[2023]

A study of 50 individuals who recovered from COVID-19 showed significant decreases in heart rate variability (HRV) parameters compared to a control group of 50 healthy individuals, indicating potential cardiac autonomic dysfunction post-recovery.

The findings suggest that HRV analysis could be a valuable tool for detecting early signs of autonomic dysfunction in patients who have recovered from COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered cardiac autonomic function after recovery from COVID-19. Kurtoğlu, E., Afsin, A., Aktaş, İ., et al.[2023]

In a study of 20 patients with new-onset postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders following COVID-19, 85% experienced ongoing symptoms 6 to 8 months after infection, highlighting the long-term impact of the virus on autonomic function.

Most patients required both non-pharmacologic and pharmacologic treatments, indicating that comprehensive management strategies are essential for addressing autonomic dysfunction after COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients. Blitshteyn, S., Whitelaw, S.[2021]

In a study involving 15 participants with post-acute sequela of COVID-19 (PASC), 15 with postural tachycardia syndrome (POTS), and 11 matched controls, significant autonomic dysfunction was observed in both conditions, including reduced cerebral blood flow velocity and small fiber neuropathy.

Correlation-based network analysis (NA) effectively differentiated between PASC and POTS by highlighting the roles of vascular and inflammatory markers, suggesting that this method can enhance our understanding of the autonomic nervous system's involvement in these complex diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network autonomic analysis of post-acute sequelae of COVID-19 and postural tachycardia syndrome. Novak, P., Giannetti, MP., Weller, E., et al.[2022]

Cardiovascular dysautonomia, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), was found in 15.21% of recently recovered COVID-19 patients, indicating a notable prevalence of these conditions post-infection.

The study identified that heart rate variability (HRV), specifically the RMSSD measure, was significantly lower in post COVID-19 patients compared to healthy controls, suggesting a potential biomarker for cardiovascular dysautonomia in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence. Shah, B., Kunal, S., Bansal, A., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0953620525004078

Short and long term effects of a two-week transcutaneous ... Interestingly, POTS patients who initially showed lower levels of cardiac vagal modulation displayed a blunted increase in heart rate upon ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11867165/

Tragus Nerve Stimulation Attenuates Postural Orthostatic ... LL-TS may be a promising therapeutic approach for attenuating autonomic imbalance in patients with POTS following COVID-19 infection.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10932945/

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia ... Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05421208?cond=Post-Acute%20COVID19%20Syndrome&limit=100&aggFilters=status:rec&rank=74

NCT05421208 | Cardiovascular Autonomic and Immune ... Aim 1 of the study is to test the hypothesis that reduced PNS activity is associated with persistent inflammation in patients with post-COVID-19 POTS. Aim 2: ...

5. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT05421208

Vanderbilt Clinical Trials - Post-COVID-19 POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12534353/

Feasibility and acceptance of transdermal auricular vagus ... The treatment was found to be safe, with no significant side effects reported; however, further research with larger study groups is needed to ...

7. bioelecmed.biomedcentral.com bioelecmed.biomedcentral.com/articles/10.1186/s42234-023-00121-6

Impaired parasympathetic function in long-COVID postural ... This case-control study investigated potential differences in autonomic cardiovascular regulation between LCP patients and healthy controls.