Post-Acute COVID-19 SyndromePhase 2NCT07189936
Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS
A Phase 2 study testing To Measure levels of circulating monocyte/ T cell doublets at Baseline, To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment and To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA in people with Post-Acute COVID-19 Syndrome and Postural Tachycardia Syndrome (POTS), run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-Acute COVID-19 Syndrome, Postural Tachycardia Syndrome (POTS), SARS CoV 2 Infection
- What is being tested?
- To Measure levels of circulating monocyte/ T cell doublets at Baseline, To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment and To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Dec 2025to 30 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- 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.
- Documented by health care provider in clinical note or encounter.
Who cannot join
- 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),
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- 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.
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cyndya Shibao
Nashville, Tennessee, 37027
Marwa Mohamed, Phd, 615-970-2384, marwa.mohamed@vumc.org
Tatiana Solis, MPH, 615 322 3447, tatiana.x.solis.montenegro.1@vumc.org
About this study
Official title: Mechanism of Isolevuglandin-Protein Adduct Formation in Persistent Immune Activation in Long COVID POTS
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.
Read more
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
Read the detailed description
Background:
Decreased parasympathetic activity is present in LCPOTS; this system is an important modulator of NAPDH oxidase activity because the activation of NADPH oxidase in monocytes promotes superoxide (reactive oxygen species -ROS) production.Oxidative stress occurs when ROS are generated in excess of normal antioxidants. Oxidative stress occurs when reactive oxygen species (ROS) are generated in excess of normal antioxidantsOxidative stress occurs when reactive oxygen species (ROS) are generated in excess of normal antioxidants that can cause harm by having adverse effects on T cell function. Targeting downstream damaging effects of ROS is an attractive alternative.
Rationale and Specific Aims
Reduced parasympathetic activity increases the production of highly immunogenic neoantigens, Isolevuglandins (IsoLG-adducts), through heightened activation of NADPH oxidase. Previous findings demonstrated that the cholinergic enhancer galantamine, reduces NADPH oxidase activation and that vagal stimulation reduces IsoLG-adducts in immune cells of LCPOTs patients.
Immune activation in response to viral or likely self-antigen presentation can induce formation of circulating monocyte/T cell complexes(doublets).The presence of these doublets provides powerful insights into the persistent and unresolved immune response that continues after the initial infection. The preliminary data show that: 1) LCPOTS subjects have markedly increased circulating doublets compared to controls; 2) T cells in these doublets produce higher levels of inflammatory cytokines IL-17A and IFN-ɣ than singlet T cells; and 3) inflammatory cytokines positively associate with the severity of orthostatic tachycardia in LCPOTS.
Monocytes in these doublets exhibit high levels of IsoLGs. These results support the hypothesis that LCPOTS represents a condition of unresolved immune activation due to IsoLG-adducts, which we have shown can act as neoantigens.
Study Aims Aim 1: To test the hypothesis that IsoLG-adducts directly contribute to persistent immune activation as measured by elevated monocyte/T cell doublets in LCPOTS.
For this purpose, the effect of 28-day treatment with Iso-LG-adduct scavenger, 2-hydroxybenzylamine (2-HOBA) versus placebo will be tested on circulating monocyte/ T cell doublets, and inflammatory cytokines.
Aim 2: To test the hypothesis that IsoLG-adducts directly contribute to splanchnic vasodilation, orthostatic tachycardia, and symptom burden in LCPOTS.
Aim 2 will be tested using the same experimental design as Aim 1 but will be focused on assessing changes in splanchnic venous capacitance with 2-HOBA treatment.
The proposed study will determine if IsoLG-adducts contribute to persistent immune activation, increased splanchnic venous capacitance, and orthostatic tachycardia in LCPOTS. The goal is to discover new treatment pathways for this disabling disease.
Study population: Total of 50 LCPOTS patients
Study visits: 3 in person study visits and 1 telemedicine
Study Interventions 2-HOBA: 2-hydroxybenzylamine, an IsoLGs potent scavenger.
Safety of 2-HOBA: 2-HOBA was found to be non-cytotoxic and non-mutagenic. It showed a low risk of QT prolongation. Two phase I studies on healthy subjects showed no serious side effects from 2-HOBA at doses ranging from 50 mg to 825 mg. Adverse events (AEs) reported were minor (e.g., headache, sleepiness, abdominal bloating) and were not dose-dependent.
2-HOBA is considered safe for healthy humans.
Dose: A dose of 500 mg three times daily for 28 day to study 2-HOBA for LCPOTS.
Biostatistical Considerations:
Sample size justification and study power (Aim 1). A mean percent of doublets of 5.37 and an SD of 4.28 for the LCPOTS group and a mean percent of doublets of 1.80 and an SD of 1.15 for the control group. The study is to assess for the primary comparison (2-HOBA vs. placebo). A sample size of 16 completed subjects per study arm will have 85% power to detect a 3.57 clinically meaningful difference, i.e., 5.37 versus 1.80 using a Welch t-test. Assuming a drop-out rate of 11%, we need to enroll 18 subjects to have 16 complete subjects per group. Given that subjects will be randomly assigned to two groups. The total enrollment needs to be 36 LCPOTS patients.
Sample size justification and study power (Aim 2). In a previous study, nitroglycerine produces a change from baseline in the Y-intercept of the P-V relationship of 5.7% with a standard deviation (SD) of 1.8 in healthy subjects. A clinically significant difference in the response to 2-HOBA versus placebo is assumed would be at least 35% of that produced with nitroglycerine, with conservatively slightly larger SD of 2.0. The study needs 19 patients per group to be able to reject the null hypothesis that this response difference is zero with a probability (power) of 85%. The Type I error probability associated with this test of this null hypothesis is 0.05. Assuming an attrition rate of 11%, the study needs 25 patients per treatment group. The total enrollment thus needs to be 50 LCPOTS patients.
Statistical Analyses:
The analysis population includes all randomized participants following intention-to-treat analyses.
Aim 1: For the primary comparison between 2-HOBA and placebo, a linear regression model will be used, with doublets (the primary endpoint) at the end of the 28-day treatment as the dependent variable and group indicator, baseline doublets, and other pre-specified baseline variables (age and sex) as covariates.
Aim 2: For the primary comparison between 2-HOBA versus placebo, a linear regression model will be used where splanchnic venous capacitance (SVC, primary endpoint) at the end 28-day treatment is the dependent variable and group indicator and baseline SVC and age and sex as covariates. For both aims, the null hypothesis of no group difference corresponds to the coefficient for the group indicator, which is zero. Appropriate transformation will be used on the outcome variable for the regression models when the normality assumption is violated. Other secondary endpoints will be analyzed similarly to the primary endpoint. The primary and secondary analyses will be conducted without imputing missing data. To protect privacy, subjects will receive a de-identified code. Data will be stored in a password protected, encrypted, and HIPAA compliant REDCap database.
Data and Safety Monitoring Plan:
Data and Safety Monitoring Officer (DSMO) will meet at least twice a year and review data on AEs, data quality, and study recruitment. Reports will be sent to the IRB and FDA at least yearly. Serious AEs will be reported to the FDA following guidelines using the online reporting portal.
- Conditions
- Post-Acute COVID-19 Syndrome, Postural Tachycardia Syndrome (POTS), SARS CoV 2 Infection, Long COVID19
- Being tested
- To Measure levels of circulating monocyte/ T cell doublets at Baseline, To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment, To measure levels of circulating monocyte/ T cell doublets after 28 days of Placebo treatment, To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA, To Measure Splanchnic venous capacitance after 28 days of Treatment with Placebo
- Keywords
- Long COVID
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Postural Orthostatic Tachycardia Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
To Measure levels of circulating monocyte/ T cell doublets at BaselineDrug
To determine the levels of circulating monocyte/ T cell doublets on all the LCPOTS subjects
To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatmentDrug
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
To measure levels of circulating monocyte/ T cell doublets after 28 days of Placebo treatmentDrug
The levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment and compare it to the placebo arms
To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBADiagnostic 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
To Measure Splanchnic venous capacitance after 28 days of Treatment with PlaceboDiagnostic 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
To Measure Orthostatic Tachycardia after 28 days of Treatment with 2HOBADiagnostic test
To Measure changes in Orthostatic Tachycardia after 28 days of Treatment with 2HOBA at 30 minutes of head up Tilt
To Measure Orthostatic Tachycardia after 28 days of Treatment with PlaceboDiagnostic 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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Day 0- Day 28 days
Secondary outcomes (1)
Measure the effects of 2- HOBA on Orthostatic Tachycardia at HUT
To see the effects of IsoLG-adducts (2-HOBA) on Orthostatic Tachycardia in LCPOTS subjects at 30 mins Head up Tilt (HUT) and compare it with Placebo group
Measured: Baseline (Day0) to after 28 days of study medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2025
- Study start18 Dec 2025
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Acute COVID-19 SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A two-parallel arm, double-blind, placebo-controlled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Cyndya Shibao, MD, Vanderbilt University Medical Center
- Investigators
- Cyndya Shibao, M.D, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07189936
- Sponsor's protocol ID
- 2-HOBA in POTS
- Status last verified
- Jan 2026
- First submitted
- 22 Sep 2025
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism of Isolevuglandin-Protein Adduct Formation in Persistent Immune Activation in Long COVID POTS
- ClinicalTrials.gov ID
- NCT07189936
- Acronym / sponsor ID
- 2-HOBA in POTS
- Conditions
- Post-Acute COVID-19 Syndrome, Postural Tachycardia Syndrome (POTS), SARS CoV 2 Infection, Long COVID19
- Keywords
- Long COVID
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 18 Dec 2025 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 24 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Background:
Decreased parasympathetic activity is present in LCPOTS; this system is an important modulator of NAPDH oxidase activity because the activation of NADPH oxidase in monocytes promotes superoxide (reactive oxygen species -ROS) production.Oxidative stress occurs when ROS are generated in excess of normal antioxidants. Oxidative stress occurs when reactive oxygen species (ROS) are generated in excess of normal antioxidantsOxidative stress occurs when reactive oxygen species (ROS) are generated in excess of normal antioxidants that can cause harm by having adverse effects on T cell function. Targeting downstream damaging effects of ROS is an attractive alternative.
Rationale and Specific Aims
Reduced parasympathetic activity increases the production of highly immunogenic neoantigens, Isolevuglandins (IsoLG-adducts), through heightened activation of NADPH oxidase. Previous findings demonstrated that the cholinergic enhancer galantamine, reduces NADPH oxidase activation and that vagal stimulation reduces IsoLG-adducts in immune cells of LCPOTs patients.
Immune activation in response to viral or likely self-antigen presentation can induce formation of circulating monocyte/T cell complexes(doublets).The presence of these doublets provides powerful insights into the persistent and unresolved immune response that continues after the initial infection. The preliminary data show that: 1) LCPOTS subjects have markedly increased circulating doublets compared to controls; 2) T cells in these doublets produce higher levels of inflammatory cytokines IL-17A and IFN-ɣ than singlet T cells; and 3) inflammatory cytokines positively associate with the severity of orthostatic tachycardia in LCPOTS.
Monocytes in these doublets exhibit high levels of IsoLGs. These results support the hypothesis that LCPOTS represents a condition of unresolved immune activation due to IsoLG-adducts, which we have shown can act as neoantigens.
Study Aims Aim 1: To test the hypothesis that IsoLG-adducts directly contribute to persistent immune activation as measured by elevated monocyte/T cell doublets in LCPOTS.
For this purpose, the effect of 28-day treatment with Iso-LG-adduct scavenger, 2-hydroxybenzylamine (2-HOBA) versus placebo will be tested on circulating monocyte/ T cell doublets, and inflammatory cytokines.
Aim 2: To test the hypothesis that IsoLG-adducts directly contribute to splanchnic vasodilation, orthostatic tachycardia, and symptom burden in LCPOTS.
Aim 2 will be tested using the same experimental design as Aim 1 but will be focused on assessing changes in splanchnic venous capacitance with 2-HOBA treatment.
The proposed study will determine if IsoLG-adducts contribute to persistent immune activation, increased splanchnic venous capacitance, and orthostatic tachycardia in LCPOTS. The goal is to discover new treatment pathways for this disabling disease.
Study population: Total of 50 LCPOTS patients
Study visits: 3 in person study visits and 1 telemedicine
Study Interventions 2-HOBA: 2-hydroxybenzylamine, an IsoLGs potent scavenger.
Safety of 2-HOBA: 2-HOBA was found to be non-cytotoxic and non-mutagenic. It showed a low risk of QT prolongation. Two phase I studies on healthy subjects showed no serious side effects from 2-HOBA at doses ranging from 50 mg to 825 mg. Adverse events (AEs) reported were minor (e.g., headache, sleepiness, abdominal bloating) and were not dose-dependent.
2-HOBA is considered safe for healthy humans.
Dose: A dose of 500 mg three times daily for 28 day to study 2-HOBA for LCPOTS.
Biostatistical Considerations:
Sample size justification and study power (Aim 1). A mean percent of doublets of 5.37 and an SD of 4.28 for the LCPOTS group and a mean percent of doublets of 1.80 and an SD of 1.15 for the control group. The study is to assess for the primary comparison (2-HOBA vs. placebo). A sample size of 16 completed subjects per study arm will have 85% power to detect a 3.57 clinically meaningful difference, i.e., 5.37 versus 1.80 using a Welch t-test. Assuming a drop-out rate of 11%, we need to enroll 18 subjects to have 16 complete subjects per group. Given that subjects will be randomly assigned to two groups. The total enrollment needs to be 36 LCPOTS patients.
Sample size justification and study power (Aim 2). In a previous study, nitroglycerine produces a change from baseline in the Y-intercept of the P-V relationship of 5.7% with a standard deviation (SD) of 1.8 in healthy subjects. A clinically significant difference in the response to 2-HOBA versus placebo is assumed would be at least 35% of that produced with nitroglycerine, with conservatively slightly larger SD of 2.0. The study needs 19 patients per group to be able to reject the null hypothesis that this response difference is zero with a probability (power) of 85%. The Type I error probability associated with this test of this null hypothesis is 0.05. Assuming an attrition rate of 11%, the study needs 25 patients per treatment group. The total enrollment thus needs to be 50 LCPOTS patients.
Statistical Analyses:
The analysis population includes all randomized participants following intention-to-treat analyses.
Aim 1: For the primary comparison between 2-HOBA and placebo, a linear regression model will be used, with doublets (the primary endpoint) at the end of the 28-day treatment as the dependent variable and group indicator, baseline doublets, and other pre-specified baseline variables (age and sex) as covariates.
Aim 2: For the primary comparison between 2-HOBA versus placebo, a linear regression model will be used where splanchnic venous capacitance (SVC, primary endpoint) at the end 28-day treatment is the dependent variable and group indicator and baseline SVC and age and sex as covariates. For both aims, the null hypothesis of no group difference corresponds to the coefficient for the group indicator, which is zero. Appropriate transformation will be used on the outcome variable for the regression models when the normality assumption is violated. Other secondary endpoints will be analyzed similarly to the primary endpoint. The primary and secondary analyses will be conducted without imputing missing data. To protect privacy, subjects will receive a de-identified code. Data will be stored in a password protected, encrypted, and HIPAA compliant REDCap database.
Data and Safety Monitoring Plan:
Data and Safety Monitoring Officer (DSMO) will meet at least twice a year and review data on AEs, data quality, and study recruitment. Reports will be sent to the IRB and FDA at least yearly. Serious AEs will be reported to the FDA following guidelines using the online reporting portal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- A two-parallel arm, double-blind, placebo-controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Levels of circulating monocyte/ T cell doublets, and inflammatory cytokines in 2 HoBA Vs Placebo | Placebo comparator | 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 treatmentto 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 |
| Effect of 2HOBA on Splanchnic venous capacitance and compare with placebo group on POTS patients | Placebo comparator | 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 PlaceboTo 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 |
| Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt | Active comparator | 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 PlaceboTo test that IsoLG-adducts directly effect Orthostatic tachycardia in LCPOTS, during 30-minute head-up tilt. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| To Measure levels of circulating monocyte/ T cell doublets at BaselineTo determine the levels of circulating monocyte/ T cell doublets on all the LCPOTS subjects | Drug | 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 treatmentSubjects 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 | 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 Placebo treatmentThe levels of circulating monocyte/ T cell doublets (immune burden) after 28 days of 2 HOBA treatment and compare it to the placebo arms | Drug | 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 2HOBAWe 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 | 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 PlaceboWe 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 | 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 2HOBATo Measure changes in Orthostatic Tachycardia after 28 days of Treatment with 2HOBA at 30 minutes of head up Tilt | Diagnostic test | 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 PlaceboTo 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 | Diagnostic test | Effect of 2HOBA on Orthostatic Tachycardia compare with placebo group during 30 minutes head up tilt |
Primary outcome
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
1 secondary outcome
Measure the effects of 2- HOBA on Orthostatic Tachycardia at HUT
Time frame: Baseline (Day0) to after 28 days of study medication
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cyndya Shibao, M.D principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing To Measure levels of circulating monocyte/ T cell doublets at Baseline, To measure levels of circulating monocyte/ T cell doublets after 28 days of 2 HOBA treatment and To Measure Splanchnic venous capacitance after 28 days of Treatment with 2HOBA in people with Post-Acute COVID-19 Syndrome and Postural Tachycardia Syndrome (POTS), run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marwa Mohamed, PhD (6159702384, marwa.mohamed@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.