Recruiting
Phase 2

2-HOBA

Sponsor:

Vanderbilt University Medical Center

Code:

NCT07602166

Conditions

Salt Sensitivity of Blood Pressure

High Blood Pressure

Inflammation

Renin-Angiotensin-Aldosterone System

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

2-hydroxybenzylamine

Placebo

Study Details

Brief summary:

Hypertension is the leading cause of preventable deaths globally, driven by complications such as myocardial infarction, stroke, heart failure, and kidney disease. Recent updates in hypertension classification by the American Heart Association (AHA) place nearly half of the U.S. population in the hypertensive category. Excess dietary salt is a major risk factor for hypertension, with 50% of hypertensive individuals exhibiting salt-sensitivity of blood pressure (SSBP). SSBP is an independent predictor of cardiovascular events and death. While kidney mechanisms in salt-sensing have been extensively studied, emerging evidence suggests that immune cells can also sense sodium (Na+).

This trial hypothesizes that myeloid cell-derived isolevuglandins (IsoLGs) drive endothelial dysfunction, perpetuating the salt-sensitive phenotype. Preliminary data indicate that targeting IsoLGs with the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) may interrupt this immune-vascular axis, reducing salt sensitivity and associated cardiovascular risks.

This phase 2 clinical trial aims to investigate the role of 2-HOBA in modulating immune cell function within blood vessels in hypertensive patients. The study will explore the impact of immunity on salt sensitivity and assess 2-HOBA's potential to reduce endothelial dysfunction, improve immune cell activation, and alleviate SSBP.

Conditions

Salt Sensitivity of Blood Pressure

High Blood Pressure

Inflammation

Renin-Angiotensin-Aldosterone System

Study ID

NCT07602166

Start date

Oct 30, 2026

Status verified date

Nov, 2026

Completion date

Jul 31, 2031

Anticipated

Primary completion date

Jul 31, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • We will perform analyses in participants previously phenotyped for SSBP, defined as a change in systolic blood pressure ≥10 mmHg from salt-loading to salt-depletion,
  • Over 18 years of age. Able to give informed consent,

Exclusion criteria:

  • Salt-resistant people,
  • Acute cardiovascular event(s) within the previous 6 months,
  • inability to understand the nature, scope, and possible consequences of the study or to participate in/comply with the protocol,
  • Current excessive alcohol or illicit drug use,
  • BP below the inclusion criteria levels after discontinuation of therapy,
  • Concomitant diabetes mellitus, type I or II,
  • Autoimmune disease,
  • Recent vaccination,
  • Younger or older than inclusion criteria,
  • Pregnant or breastfeeding
  • Women of childbearing potential unwilling to use highly effective contraceptive (see Risk section),
  • Confirmed or suspected renal, renovascular or endocrine causes of secondary hypertension,
  • Treatment with agents known to increase BP (e.g., adrenergic agonists for ADHD, SSRI and SNRI antidepressants, chronic use of decongestants or non-steroidal anti-inflammatory drugs,
  • Active or ongoing infection, including HIV/AIDS,
  • Active or ongoing malignancy with the exception of basal cell carcinoma of the skin,
  • Severe psychiatric disorders,
  • Any condition that may alter the immunological results of the study including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, giant cell arteritis, psoriasis, inflammatory bowel disease, and multiple sclerosis,
  • Use of glucocorticoids, immunosuppressants, direct immunomodulators or chemotherapeutic drugs that in the judgment of the investigators may include a major inflammatory component,
  • Individuals who have contraindications to high salt diets (e.g. heart, renal, or liver failure) or low salt diets (e.g. postural orthostatic tachycardia syndrome, prescribed salt tablets, fludrocortisone or midodrine) or 24-hr ambulatory blood pressure monitoring (e.g. women with bilateral upper extremity lymphedema following breast cancer surgeries),
  • Prior diagnosis of liver cirrhosis or the following abnormal liver function studies: AST or ALT >1.5x the upper limit of normal or total bilirubin ≥1.5 mg/dl,
  • Use of Aspirin,
  • Use of monoamine oxidase inhibitors (MAO-I),
  • Individuals with medical contraindications to certain food content,
  • Use of nitrate therapy. (Participants who are taking PDE-5 inhibitors will be instructed to discontinue use at least 48 hours prior to testing),
  • Patients with resistant hypertension, defined as above-goal blood pressure despite the concurrent use of three antihypertensive drug classes at screening, will be excluded for safety reasons,
  • Average of three office-based blood pressure readings greater than 160 mmHg systolic or 100 mmHg diastolic will not be eligible for enrollment,
  • Use of drugs such as anticoagulants (e.g., warfarin), beta-blockers, antiarrhythmics, antidepressants/antipsychotics, and other medications primarily metabolized by CYP2C9, CYP2C19, and CYP2D6 that may cause drug-drug interaction.

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: Drug-washout-placebo

Participants with salt sensitivity of blood pressure to receive treatment with 2-HOBA (500mg) three times a day for 4 weeks, followed by a washout period of 4 weeks, and then placebo for 4 weeks

experimental: Arm 2: Placebo-washout-Drug

Participants with salt sensitivity of blood pressure to receive treatment with placebo for 4 weeks followed by a washout period of 4 weeks, and then 2-HOBA (500mg) three times a day for 4 weeks.

Interventions

2-hydroxybenzylamine

2HOBA

Placebo

Placebo

Primary outcome measure

  • Change in 24-hour ambulatory systolic blood pressure (SBP) [ Time Frame: From week 0-4 and week 8-week12 ]

Central Contacts and Locations

Central contacts

Annet Kirabo, D.V.M., M.Sc., Ph.D. F.A.H.A.

615-343-0933annet.kirabo@vumc.org

Cindy Mambungu, LPN

615-343-5828cindy.a.booker@vumc.org

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Annet Kirabo, D.V.M., M.Sc., Ph.D. F.A.H.A.

615-343-0933annet.kirabo@vumc.org

Talat A Ikizler, MD

alp.ikizler@vumc.org

Principal Investigator:

Annet Kirabo, D.V.M., M.Sc., Ph.D. F.A.H.A.

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

Nov 4, 2026

Last verified

Nov, 2026

Keywords

  • salt sensitivity
  • hypertension
  • renin-angiotensin-aldosterone system
  • immune cells

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-05. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2026-11-04. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.