Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS

NCT07189936 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2-HOBA in POTS
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Post-Acute COVID-19 Syndrome; Postural Tachycardia Syndrome (POTS); SARS CoV 2 Infection; Long COVID19

Keywords

Long COVID

Outcome Measures

Primary Outcomes (2)

• Effect IsoLG-adducts (2-HOBA) measured by levels of monocyte/T cell doublets in LCPOTS.

  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

  Baseline (Day 0) to after 28 days of treatment

• Changes in Splanchnic venous capacitance before and after 28 days of treatment

  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

  Day 0- Day 28 days

Secondary Outcomes (1)

• Measure the effects of 2- HOBA on Orthostatic Tachycardia at HUT

  Baseline (Day0) to after 28 days of study medication

Study Arms (3)

Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo

PLACEBO COMPARATOR

to test the effect of 28-day treatment with Iso-LG-adduct scavenger, 2-hydroxybenzylamine (2-HOBA) versus placebo on circulating monocyte/ T cell doublets (CD14+CD3+) , and inflammatory cytokines

Drug: To Measure levels of circulating monocyte/ T cell doublets at Baseline; Drug: To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment; Drug: To measure levels of circulating monocyte/ T cell doublets after 28 days of Placebo treatment

Effect of 2HOBA on Splanchnic venous capacitance and compare with placebo group on POTS patients

PLACEBO COMPARATOR

To test the hypothesis that IsoLG-adducts directly contribute to splanchnic vasodilation, by assessing changes in splanchnic venous capacitance with 2-HOBA treatment at head up Tilt

Diagnostic Test: To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA; Diagnostic Test: To Measure Splanchnic venous capacitance after 28 days of Treatment with Placebo

Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt

ACTIVE COMPARATOR

To test that IsoLG-adducts directly effect Orthostatic tachycardia in LCPOTS, during 30-minute head-up tilt.

Diagnostic Test: To Measure Orthostatic Tachycardia after 28 days of Treatment with 2HOBA; Diagnostic Test: To Measure Orthostatic Tachycardia after 28 days of Treatment with Placebo

Interventions

To measure levels of circulating monocyte/ T cell doublets after 28 days of Placebo treatment DRUG

The levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment and compare it to the placebo arms

Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo

To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA DIAGNOSTIC_TEST

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

Effect of 2HOBA on Splanchnic venous capacitance and compare with placebo group on POTS patients

To Measure Splanchnic venous capacitance after 28 days of Treatment with Placebo DIAGNOSTIC_TEST

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

Effect of 2HOBA on Splanchnic venous capacitance and compare with placebo group on POTS patients

To Measure Orthostatic Tachycardia after 28 days of Treatment with 2HOBA DIAGNOSTIC_TEST

To Measure changes in Orthostatic Tachycardia after 28 days of Treatment with 2HOBA at 30 minutes of head up Tilt

Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt

To Measure Orthostatic Tachycardia after 28 days of Treatment with Placebo DIAGNOSTIC_TEST

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

Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt

To Measure levels of circulating monocyte/ T cell doublets at Baseline DRUG

To determine the levels of circulating monocyte/ T cell doublets on all the LCPOTS subjects

Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo

To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment DRUG

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

Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• American Heart Association: collaborator

Study Sites (1)

Cyndya Shibao

Nashville, Tennessee, 37027, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Postural Orthostatic Tachycardia Syndrome; COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• Cyndya Shibao, M.D

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marwa Mohamed, PhD

CONTACT

6159702384; marwa.mohamed@vumc.org

Cyndya Shibao, MD

CONTACT

(615)936-4584; Cyndya.shibao@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A licensed MTI BioTech (MTI) to develop 2-HOBA. MTI will provide 2-HOBA and matching placebo capsules for the study . Capsules will be shipped to the Vanderbilt Investigational Drug Services (IDS) for use in this trial. The IDS will be responsible for storage, and labeling of 2-HOBA and matching placebo, and for maintaining accurate drug storage and dispensing logs.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A two-parallel arm, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: September 24, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)