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

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

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

Sponsors & Collaborators

• American Heart Association

  collaborator OTHER

• Vanderbilt University Medical Center

  lead OTHER

Principal Investigators

• Cyndya Shibao, M.D · Vanderbilt University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-18

Primary Completion

2028-06-30

Completion

2029-06-30

FDA Drug

Yes

Countries

• United States

Study Locations