Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT06027255 |
Other study ID # |
Long COVID |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
April 1, 2024 |
Est. completion date |
October 31, 2026 |
Study information
Verified date |
March 2024 |
Source |
Vanderbilt University Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Parasympathetic nervous system (PNS) is part of the body's autonomic nervous system(PNS)
protects body against inflammation. Study shows that reduced PNS function activity is
associated with persistent inflammation.
Preliminary data from the studies shows, that post-COVID-19 POTS patients have reduced
parasympathetic (PNS) function. Given that the PNS protects against inflammation, this
clinical trial aims to prove that post-COVID-19 POTS is caused by reduced PNS activity, which
in turn, contributes to persistent inflammation, orthostatic intolerance, and OI symptoms.
The study will 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.
Description:
COVID-19 infections can cause a disabling syndrome that persists beyond the 3-month
convalescence period. The term post-acute COVID-19 syndrome or Long COVID is coined to
describe a cluster of symptoms consisting of fatigue, chest pain, reduced exercise tolerance,
tachycardia, and cognitive impairment.
Persistent tachycardia remains one of the most common complaints, reported in 9% of patients
at 6 months post-infection. These symptoms overlap with those present in patients with
Postural orthostatic tachycardia syndrome (POTS). It is noteworthy that about half of POTS
patients also report a history of viral infection prior to the development of these symptoms.
Post-COVID-19 tachycardia syndrome, POTS variant: It present with chronic tachycardia with
symptoms of orthostatic intolerance (OI) without any other 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.
Elevated levels of inflammatory markers CRP,D-dimer and IL-6 are found in Long COVID
patients. Data in POTS, which resembles post-COVID tachycardia syndrome, shows increased
cytokines including IL-6, IL-1b, and TNF-a.
Notably, stimulation of the efferent vagus nerve (PNS), has been shown to reduce
proinflammatory markers production and systemic inflammation. Hence, decreased PNS function,
as reported with acute SARS-CoV-2 infection and in post-COVID-19 POTS patients, may render
these patients prone to persistent inflammation. To determine the link between PNS activity
and immune activation in post-COVID-19 POTS, the study aims to 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.
Rationale and Specific Aims:
Preliminary data shows that post-COVID-19 POTS patients have reduced parasympathetic (PNS)
function. Given that the PNS protects against inflammation, we hypothesize that post-COVID-19
POTS is caused by reduced PNS activity, which in turn, contributes to persistent
inflammation, orthostatic intolerance, and OI symptoms.
Primary Aim: Test the hypothesis that reduced PNS activity is associated with persistent
inflammation in patients with post-COVID-19 POTS.
Study Participants:
This is a cross-sectional study conducted, up to 150 patients will be enrolled, 50 POTS
without Long-COVID, 50 POTS with Long-COVID and 50 controls with history of COVID-19
infection without sequelae.
Study Procedures
Recruitment: Subjects will be recruited from referrals to the Vanderbilt Autonomic
Dysfunction Center (ADC)
Study visit:
Assessments:
- Autonomic symptoms assessment questionnaire (COMPASS-31)
- Quality of life EQ-5D
- PROMIS scale (Functional Activities Questionnaire in Older Adults with Dementia),
- OHQ (Orthostatic Hypotension Questionnaire)
- CBS (Cambridge Brain sciences: Web based cognitive assessment platform, Optional), and
neuropsychological tests Blood sample collection: CBC, CMP, C-reactive protein (CRP),
D-dimer, Flow cytometry study, PBMC isolation Autonomic function tests: Testing
performed at Vanderbilt ADC within 10 years of the study visit will be utilized. Testing
will not be repeated solely for the purposes of this study.
Statistical Considerations
Biostatistical Section The primary endpoint serum IL-6. The proposed sample size of 150 (50
POTD, 50 Long COVID POTS patients and 50 controls) provides more than 90% power to detect an
effect size of 0.62 for the mean difference in IL-6 between post-COVID-19 POTS (cases) and
controls (COVID-19 infected w/o sequelae), with the two-sided type I error = 5%. This
calculation is based on the preliminary data of mean difference of IL-6 ≈ 1.82 and the SD ≈
2.94 in POTS.16 The effect size is defined as the ratio of mean IL-6 difference between cases
and controls to standard deviation.
Data analysis plan: Demographic information will be tabulated. Descriptive statistics,
including means, standard deviations, and ranges for continuous parameters, as well as
percent and frequencies for categorical parameters, will be presented. T-test or Mann-Whitney
(as appropriate) will be applied to examine the mean differences between cases and control
with respect to the outcomes. The conditional logistic regression model will be applied for
the multivariable data analysis. The adjusted p-values and the adjusted 95% confidence
intervals (CIs) will be reported.