Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans
1 other identifier
interventional
20
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2026
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 15, 2026
CompletedFirst Posted
Study publicly available on registry
May 22, 2026
CompletedStudy Start
First participant enrolled
July 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2031
Study Completion
Last participant's last visit for all outcomes
July 1, 2031
May 22, 2026
May 1, 2026
5 years
May 15, 2026
May 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in 24-hour ambulatory systolic blood pressure (SBP)
Measurement of salt sensitivity of blood pressure before and after each treatment period (2-HOBA and placebo), using a standardized inpatient salt-loading and salt-depletion protocol.
From week 0-4 and week 8-week12
Secondary Outcomes (3)
FMD
From baseline to week 4, from Week 8 to week 12.
Measurement of oxidative stress and inflammatory cytokines in blood and endothelial cells
Week 0, 4, 8 and 12.
Endothelial Cell Harvesting and Analysis
From week 0-4 and week 8-12
Study Arms (2)
Arm 1: Drug-washout-placebo
EXPERIMENTALParticipants with salt sensitivity of blood pressure
Arm 2: Placebo-washout-Drug
EXPERIMENTALParticipants with salt sensitivity of blood pressure
Interventions
Eligibility Criteria
You may qualify if:
- 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,
You may not qualify if:
- 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,
- Concomitant diabetes mellitus, type I or II,
- Autoimmune disease,
- Recent vaccination,
- 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,
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Related Publications (9)
Weinberger MH. Salt sensitivity is associated with an increased mortality in both normal and hypertensive humans. J Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4):274-6. doi: 10.1111/j.1524-6175.2002.00924.x.
PMID: 12147930RESULTErtuglu LA, Pitzer Mutchler A, Jamison S, Laffer CL, Elijovich F, Saleem M, Blackwell DJ, Kryshtal DO, Egly CL, Sahinoz M, Sheng Q, Wanjalla CN, Pakala S, Yu J, Gutierrez OM, Kleyman TR, Knollmann BC, Ikizler TA, Kirabo A. Eicosanoid-Regulated Myeloid ENaC and Isolevuglandin Formation in Human Salt-Sensitive Hypertension. Hypertension. 2024 Mar;81(3):516-529. doi: 10.1161/HYPERTENSIONAHA.123.21285. Epub 2023 Sep 7.
PMID: 37675576RESULTWeinberger MH. Salt sensitive human hypertension. Endocr Res. 1991;17(1-2):43-51. doi: 10.1080/07435809109027188.
PMID: 1879381RESULTWeinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001 Feb;37(2 Pt 2):429-32. doi: 10.1161/01.hyp.37.2.429.
PMID: 11230313RESULTWeinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986 Jun;8(6 Pt 2):II127-34. doi: 10.1161/01.hyp.8.6_pt_2.ii127.
PMID: 3522418RESULTLuft FC, Miller JZ, Grim CE, Fineberg NS, Christian JC, Daugherty SA, Weinberger MH. Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses. Hypertension. 1991 Jan;17(1 Suppl):I102-8. doi: 10.1161/01.hyp.17.1_suppl.i102.
PMID: 1846122RESULTWeinberger MH, Fineberg NS. Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Hypertension. 1991 Jul;18(1):67-71. doi: 10.1161/01.hyp.18.1.67.
PMID: 1860713RESULTErtuglu LA, Demirci M, Mutchler AL, Laffer CL, Saleem M, Ikizler TA, Kirabo A. Antigen-Presenting Cell Isolevuglandins Link Salt Sensitivity of Blood Pressure to Insulin Resistance. J Clin Endocrinol Metab. 2026 Mar 17;111(4):1091-1097. doi: 10.1210/clinem/dgaf556.
PMID: 41052782RESULTErtuglu LA, Pitzer Mutchler A, Elijovich F, Laffer CL, Sheng Q, Wanjalla CN, Kirabo A. Regulation of human salt-sensitivite hypertension by myeloid cell renin-angiotensin-aldosterone system. Front Physiol. 2023 Jul 18;14:1208270. doi: 10.3389/fphys.2023.1208270. eCollection 2023.
PMID: 37534363RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Medicine Associate Professor of Molecular Physiology and Biophysics Division of Clinical Pharmacology Department of Medicine
Study Record Dates
First Submitted
May 15, 2026
First Posted
May 22, 2026
Study Start (Estimated)
July 1, 2026
Primary Completion (Estimated)
July 1, 2031
Study Completion (Estimated)
July 1, 2031
Last Updated
May 22, 2026
Record last verified: 2026-05