2-HOBA in Systemic Lupus Erythematosus

Scavenging IsoLGs in Autoimmune Disease: a Proof-of-concept Clinical Study

This is a phase II randomized, placebo-controlled, double-blind, cross-over study to determine the effect of isolevuglandin (IsoLG) scavenging by 2-HOBA on blood pressure and immune activation in patients with SLE. 42 patients with stable SLE will be randomized to treatment sequence to receive placebo or 500mg 2-HOBA three times a day for 8 weeks followed by a 4 week washout and then 8 weeks of the other agent.

Primary outcome measures include change in 24-hour blood pressure and NETosis. This study will provide mechanistic information on the role of IsoLGs in autoimmune disease-associated hypertension and immune activation.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erthematosus (SLE)
• Intervention / Treatment: Drug: 2-HOBA acetate (2-Hydroxybenzlamine acetate); Drug: Placebo

Detailed Description

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease with a markedly increased prevalence of not only hypertension but also resistant hypertension. Hypertension, along with other factors, leads to a 2 to 3-fold increase in risk of cardiovascular disease in SLE. Other than glucocorticoids and immunosuppression, there are few therapeutic options for patients with SLE and none that are known to have a beneficial effect on hypertension and cardiovascular disease; in fact, glucocorticoids have substantial deleterious effects. The increased prevalence of hypertension and its greater severity in SLE patients are unexplained; however, work from our group and others increasingly implicates activation of the immune system in the pathogenesis of hypertension. Moreover, our data suggest that downstream products of oxidative stress, specifically isolevuglandins (IsoLGs), drive immune activation and hypertension.

IsoLGs are highly reactive dicarbonyl products of oxidative stress that bind covalently to proteins causing conformational changes rendering them immunogenic and proinflammatory. Two decades of work at Vanderbilt led to the identification of 2-hydroxybenzylamine (2-HOBA) as a highly effective scavenger of reactive dicarbonyls such as IsoLGs. Scavenging reactive dicarbonyls is preferable to using antioxidants because reactive oxygen species are necessary for normal cellular function. In animal models of SLE, hypertension, and atherosclerosis 2-HOBA reduced inflammation, neutrophil extracellular traps (NETosis), blood pressure, and atherosclerosis, and in human phase I clinical studies with healthy volunteers it was well tolerated.

This is a mechanistic, proof-of-concept phase II study with a randomized, placebo-controlled, double-blind, cross-over design to determine the effect of IsoLG scavenging by 2-HOBA on blood pressure and immune activation in patients with SLE. 42 patients with stable SLE will be randomized to treatment sequence to receive placebo or 500mg 2-HOBA three times a day for 8 weeks followed by a 4 week washout and then 8 weeks of the other agent. Comparing 2-HOBA and placebo arms, primary outcomes include change in 24-hour blood pressure and immune activation measured by NETosis.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Phicharmon Kulapatana (study coordinator); Phone Number: 615-936-5747; Email: phicharmon.kulapatana@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Phicharmon Kulapatana; Phone Number: 615-936-5747; Email: phicharmon.kulapatana@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent
• Age ≥18 years
• Female (biological)
• Meeting the 2019 European League Against Rheumatism/ American College of Rheumatology classification criteria for SLE32
• No change in immunosuppressants ≥3 months
• Stable prednisone (or equivalent) dose ≤ 20mg/ day for ≥ 1 month
• Elevated blood pressure defined as >120 and < or = 160 mmHg systolic or >80 and < or = 110 mmHg diastolic blood pressure at screening visit
• No change in anti-hypertensive dose ≥2 weeks
• Willingness to stop NSAIDs for ≥2 weeks before and throughout the study
• If of childbearing potential, willingness to use effective birth control throughout the study and 4 weeks after completion of the study (examples: condom, diaphragm, oral contraceptive pill, intrauterine device)

Exclusion Criteria:

• Pregnant or breastfeeding
• Male (biological)
• Active cancer except for non-melanoma skin cancer
• 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
• Active infection requiring medical intervention
• Major surgery in ≤ 3 months
• Aspirin allergy
• Use of MAO-I
• Estimated creatinine clearance <30 ml/min
• Known atrial fibrillation
• Severe comorbid condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo First; Placebo for first 8 weeks, then washout for 4 weeks, and then 2-HOBA acetate for 8 weeks	Drug: 2-HOBA acetate (2-Hydroxybenzlamine acetate); 2-HOBA acetate (2-Hydroxybenzlamine acetate) 500mg (provided as two 250mg capsules) three times per day; Other Names: 2-hydroxybenzylamine; salicylamine; IUPAC name: 2-(aminomethyl)phenol; 2-HOBA; Drug: Placebo; Placebo (provided as two capsules) three times per day; Other Names: indentical placebo
Experimental: 2-HOBA First; 2-HOBA acetate for first 8 weeks, then washout for 4 weeks, and then placebo for 8 weeks	Drug: 2-HOBA acetate (2-Hydroxybenzlamine acetate); 2-HOBA acetate (2-Hydroxybenzlamine acetate) 500mg (provided as two 250mg capsules) three times per day; Other Names: 2-hydroxybenzylamine; salicylamine; IUPAC name: 2-(aminomethyl)phenol; 2-HOBA; Drug: Placebo; Placebo (provided as two capsules) three times per day; Other Names: indentical placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour systolic blood pressure	Investigators will measure change in 24-hour systolic blood pressure	Measured at the beginning and end of each phase at weeks 0, 8, 12, and 20.
NETosis	Investigators will measure change in NETosis by ELISA assessing circulating NET concentration	Measured at beginning and end of each phase at weeks 0, 8, 12, and 20.

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Michelle J Ormseth, MD, MSCI, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: November 4, 2025
• First Submitted That Met QC Criteria: November 4, 2025
• First Posted (Actual): November 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hypertension; systemic lupus erythematosus; SLE; blood pressure; oxidative stress; lupus; NETosis; isolevuglandins
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Hypertension; 2-(aminomethyl)phenol
• Other Study ID Numbers: 250944; 1P01HL174442-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The following data files will be produced:

• Demographic/ clinical data such as age, race, sex, SLE disease activity measures, and medication use
• Standard clinical laboratory measurements such as complete blood count, complete metabolic panel, complement C3 and C4, dsDNA antibody titer, erythrocyte sedimentation rate, urinalysis, spot urine protein and creatinine.
• 24-hour blood pressure measurements
• NETosis data
• type 1 interferon signature Identifiable data will be de-identified and anonymized prior to sharing. Given the rarity of the disease, small geographic area of recruitment, and very specific manifestations of SLE in individual patients, the risk of re-identification of participants is real. Thus, to ensure privacy concordant with the requirements of the institutional review board, information on specific SLE manifestations will not be shared and demographic variables with few participants may be collapsed/ aggregated (e.g. age, race) to anonymize data.

• IPD Sharing Time Frame: Data will be made available upon publication of study results or end of the performance period, whichever comes first. The data shared will be archived and available on the Vivli platform for request by researchers for a minimum of 10 years after contribution.
• IPD Sharing Access Criteria: The Vivli platform has multiple levels of protection for managing human participant data. Each user must sign a Data Use Agreement and there is an established policy for managing violations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No