NCT07189936 · Vanderbilt University Medical Center
Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS
What this study is about
Long COVID is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. Approximately 7% of individuals who recover from SARS-Cov-2 infection develop Long COVID.
View original scientific description
Long COVID is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. Approximately 7% of individuals who recover from SARS-Cov-2 infection develop Long COVID. Long COVID Postural Orthostatic Tachycardia Syndrome (LCPOTS) symptoms include fatigue, exercise intolerance, orthostatic intolerance, syncope, and heightened orthostatic tachycardia. Research has found that decreased parasympathetic activity in LCPOTS increases the production of highly immunogenic neoantigens Isolevuglandins (IsoLG-adducts). IsoLG-adducts induce formation of circulating monocyte/T cell complexes(doublets) leading to the persistent and unresolved immune response that continues after the initial infection.
Interventions
DRUG
To Measure levels of circulating monocyte/ T cell doublets at Baseline
To determine the levels of circulating monocyte/ T cell doublets on all the LCPOTS subjects
DRUG
To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment
Subjects will be randomized 1:1 to 2-HOBA or matching placebo. The levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment
DRUG
To measure levels of circulating monocyte/ T cell doublets after 28 days of Placebo treatment
The levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment and compare it to the placebo arms
DIAGNOSTIC_TEST
To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA
We will Measure changes in Splanchnic venous capacitance after 28 days of Treatment with 2HOBA and compare it with baseline during 30 Mins head up tilt . All the LCPOTS subjects will be randomized 1:1 to 2-HOBA or matching placebo
DIAGNOSTIC_TEST
To Measure Splanchnic venous capacitance after 28 days of Treatment with Placebo
We will Measure changes in splanchnic venous capacitance during 30 mins head up tilt ,after 28 days of Treatment with Placebo, we will compare it to the subjects who received 2 HOBA for 28 days
DIAGNOSTIC_TEST
To Measure Orthostatic Tachycardia after 28 days of Treatment with 2HOBA
To Measure changes in Orthostatic Tachycardia after 28 days of Treatment with 2HOBA at 30 minutes of head up Tilt
DIAGNOSTIC_TEST
To Measure Orthostatic Tachycardia after 28 days of Treatment with Placebo
To Measure changes in Orthostatic Tachycardia after 28 days of Treatment with Placebo at 30 minutes of head up Tilt and compare it with the subjects who received 28 days of 2HOBA
Primary outcome measures
Effect IsoLG-adducts (2-HOBA) measured by levels of monocyte/T cell doublets in LCPOTS.
Time frame: Baseline (Day 0) to after 28 days of treatment
The effect of 28-day treatment with Iso-LG-adduct scavenger, 2-hydroxybenzylamine (2-HOBA) versus placebo on circulating monocyte/ T cell doublets, and inflammatory cytokines and compare it to the placebo
Changes in Splanchnic venous capacitance before and after 28 days of treatment
Time frame: Day 0- Day 28 days
Changes in Splanchnic venous capacitance at 30 mins Head up tilt, before and after 28 days of treatment and compare it with 2-HOBA group with placebo group
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- All participants should meet diagnostic criteria for Long COVID and POTS and as outlined below: Long COVID (LC) is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. POTS: the presence of chronic symptoms lasting more than 3 months, along with orthostatic tachycardia (a HR increase over 30 bpm upon standing or exceeding 120 bpm without orthostatic hypotension) within 10 minutes upon standing or 75-degree head up tilt. For patients aged 18 and 21, an increase of more than 40 bpm or a standing HR over 130 bpm will be required for inclusion in the study. 2 Patients need confirmation of POTS diagnosis based on orthostatic vital signs obtained prior to enrollment in the study. SARS-CoV-2 infection 3 or more months prior identified by the follow signs: A. Meets the clinical OR epidemiological criteria.
- Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia.
- Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or C. Presents with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test. D. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or E. Meeting clinical criteria AND/OR epidemiological criteria (See A). With a positive professional use or self-test, SARS-CoV-2 Antigen-Rapid Diagnostic Test. F. Documented by health care provider in clinical note or encounter.
Exclusion criteria
- Known active acute SARS-Cov-2 infection (4 weeks from onset)
- Moderate or severe immunocompromised patients,
- Known history of cardiovascular disease (atrioventricular block (AV block), myocardial infarction, angina, heart failure, pacemaker, stroke, transient ischemic attack within 6 months before enrollment),
- Uncontrolled hypertension (BP\>140/90 despite appropriate treatment);
- Type 1 or type 2 diabetes mellitus;
- Impaired hepatic function (AST or ALT greater than 1.5x the upper limit of normal or with total bilirubin ≥1.5mg/dl),
- Impaired renal function test (eGFR\<60 mL/min/1.73m2),
- Anemia (hemoglobin \<10 g/dl),
- Pregnant or breastfeeding women,
- Known history of autoimmune disease, steroid use or other immunotherapies,
- Inability to provide informed consent. We will also exclude individuals with known allergy sensitivity to components of the study medication, known contraindication to the study interventions, use of central acetylcholinesterase inhibitors (e.g., pyridostigmine, donezepil), aspirin allergy because salicylic acid is a metabolite of 2-HOBA; use of monoamine oxidase inhibitors (MAO-I) because of some inhibition of MAO-A is present in the anticipated therapeutic range of 2-HOBA. \-
Where
- Nashville, Tennessee
Collaborators
American Heart Association
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jan 22, 2026 · Source of record for eligibility and locations