NCT05421208

Brief Summary

The term post-acute COVID-19 syndrome or Long COVID is a disabling syndrome that persists beyond the 3-month convalescence period after COVID-19 infections. This syndrome affects mostly women (\~80%), present with chronic tachycardia and Orthostatic intolerance symptoms without any identifiable cause. In addition, non-specific symptoms such as fatigue, headache, and "brain fog", commonly described in POTS patients are also present in this novel condition, recently named post-COVID-19 tachycardia syndrome, POTS variant. Reduced Vagal activity and unresolved inflammation is post-COVID-19 POTS is hypothesized as the cause of Long COVID

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
14mo left

Started Jun 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress77%
Jun 2022Jun 2027

Study Start

First participant enrolled

June 1, 2022

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

June 14, 2022

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 16, 2022

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

January 20, 2026

Status Verified

January 1, 2026

Enrollment Period

4.1 years

First QC Date

June 14, 2022

Last Update Submit

January 15, 2026

Conditions

Keywords

SARS-CoV-2 infection

Outcome Measures

Primary Outcomes (1)

  • IL-6 levels

    Evaluate immune cell activation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity. The primary endpoint is IL-6 levels

    Baseline to after 28 days of tVNS stimulation

Secondary Outcomes (1)

  • Orthostatic Symptoms Score

    Baseline to after 28 days of tVNS stimulation

Study Arms (2)

Compare inflammatory markers (IL-6) in post- COVID 19 POTS patients with Controls

EXPERIMENTAL

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

Diagnostic Test: Levels of inflammatory cytokine ( IL-6) in post-COVID-19 POTS and controlsDiagnostic Test: Levels of inflammatory cytokine ( IL-6) in controls

Effect of OI symptoms & inflmmation after Restoring PNS functions in post-COVID POTS patients.

EXPERIMENTAL

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

Diagnostic Test: Effect on inflammation after chronic PNS stimulation

Interventions

Inflammatory and immune profile of post-COVID-19 POTS patients. Reduced PNS activity (vagal tone) in relation to persistent inflammation.

Compare inflammatory markers (IL-6) in post- COVID 19 POTS patients with Controls

Inflammatory and immune profile of healthy controls. Controls are the subjects who recovered from COVID-19 infection with no sequelae.

Compare inflammatory markers (IL-6) in post- COVID 19 POTS patients with Controls

Inflammatory biomarkers after restoring PNS function in post-COVID-19 POTS patients, by chronic transcutaneous vagus nerve stimulation (tVNS) in post COVID-19 POTS patients

Effect of OI symptoms & inflmmation after Restoring PNS functions in post-COVID POTS patients.

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Prior RT-PCR-confirmed COVID-19 infection.
  • Post-COVID-19 POTS will be defined as the presence of orthostatic tachycardia (\>30 bpm) and chronic (\>3 months) pre-syncopal symptoms.

You may not qualify if:

  • Heart Disease: Myocardial Infarction, angina, heart failure
  • History of stroke, or transient ischemic attack
  • Undergone an invasive procedure for CVD (coronary artery bypass graft, angioplasty, valve replacement, pacemaker placement or other vascular surgeries)
  • Uncontrolled hypertension defined as persistent blood pressure \>140/90.
  • Post-menopausal women.
  • Diabetes Mellitus Type 1 or Type 2. ,
  • Impaired Hepatic function
  • Impaired renal function test (eGFR\<60 mL/min/1.73m2).
  • Ongoing substance abuse.
  • Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study.
  • History of seizures.
  • Chronic use of steroids, NSAIDs.
  • On biologics such as anti-IL6 (omalizumab) and anti-TNF-alpha drugs
  • Pregnancy or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 SyndromePostural Orthostatic Tachycardia SyndromeCOVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesPost-Infectious DisordersChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsOrthostatic IntolerancePrimary DysautonomiasAutonomic Nervous System DiseasesNervous System Diseases

Study Officials

  • Cyndya Shibao, M.D

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Meena Vinayagam, M.D.

CONTACT

Cyndya Shibao, MD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
The POTS patients will be randomized to chronic transcutaneous vagus nerve stimulation (tVNS) in any of the two sites on ear, and there will 50% change to be allocated to one of the sites that may have less stimulation.
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Model Details: Case-control study
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

June 14, 2022

First Posted

June 16, 2022

Study Start

June 1, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Last Updated

January 20, 2026

Record last verified: 2026-01

Locations