Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS
Mechanism of Isolevuglandin-Protein Adduct Formation in Persistent Immune Activation in Long COVID POTS
Vanderbilt University Medical Center
50 participants
Dec 18, 2025
INTERVENTIONAL
Conditions
Summary
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. The purpose of the this research, is to study the effects of 2-hydroxybenzylamine (2-HOBA), an Iso-LG-adduct scavenger, its effects in immune markers and compare it with Placebo
Eligibility
Inclusion Criteria11
- 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.
- 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 Criteria13
- 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.
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Interventions
To determine the levels of circulating monocyte/ T cell doublets on all the LCPOTS subjects
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
The levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment and compare it to the placebo arms
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
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
To Measure changes in Orthostatic Tachycardia after 28 days of Treatment with 2HOBA at 30 minutes of head up Tilt
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
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07189936