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Mechanism of Isolevuglandin-Protein Adduct Formation in Persistent Immune Activation in Long COVID POTS

Status: Recruiting
Location: See location...
Intervention Type: Diagnostic test, Drug
Study Type: Interventional
Study Phase: Phase 2
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

⁃ 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.

Locations
United States
Tennessee
Cyndya Shibao
RECRUITING
Nashville
Contact Information
Primary
Marwa Mohamed, PhD
marwa.mohamed@vumc.org
6159702384
Backup
Cyndya Shibao, MD
Cyndya.shibao@vumc.org
(615)936-4584
Time Frame
Start Date: 2025-12-18
Estimated Completion Date: 2029-06-30
Participants
Target number of participants: 50
Treatments
Placebo_comparator: Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo
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
Placebo_comparator: Effect of 2HOBA on Splanchnic venous capacitance and compare with placebo group on POTS patients
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
Active_comparator: Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt
To test that IsoLG-adducts directly effect Orthostatic tachycardia in LCPOTS, during 30-minute head-up tilt.
Sponsors
Leads: Vanderbilt University Medical Center
Collaborators: American Heart Association

This content was sourced from clinicaltrials.gov