2-HOBA in Systemic Lupus Erythematosus

NCT ID: NCT07225543

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-15
• Study Completion Date: 2030-07-31

Brief Summary

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 750mg 2-HOBA three times a day for 4 weeks followed by a 4 week washout and then 4 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.

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 750mg 2-HOBA three times a day for 4 weeks followed by a 4 week washout and then 4 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.

Conditions

Systemic Lupus Erthematosus (SLE)

Keywords

systemic lupus erythematosus; SLE; lupus; oxidative stress; hypertension; blood pressure; NETosis; isolevuglandins

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo First

Placebo for first 4 weeks, then washout for 4 weeks, and then 2-HOBA acetate for 4 weeks

Group Type: EXPERIMENTAL

2-HOBA acetate (2-Hydroxybenzlamine acetate)

Intervention Type: DRUG

2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day

Placebo

Intervention Type: DRUG

Placebo (provided as three capsules) three times per day

2-HOBA First

2-HOBA acetate for first 4 weeks, then washout for 4 weeks, and then placebo for 4 weeks

Group Type: EXPERIMENTAL

2-HOBA acetate (2-Hydroxybenzlamine acetate)

Intervention Type: DRUG

2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day

Placebo

Intervention Type: DRUG

Placebo (provided as three capsules) three times per day

Interventions

2-HOBA acetate (2-Hydroxybenzlamine acetate)

2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day

Intervention Type: DRUG

Placebo

Placebo (provided as three capsules) three times per day

Intervention Type: DRUG

Other Intervention Names

2-hydroxybenzylamine; 2-HOBA; salicylamine; IUPAC name: 2-(aminomethyl)phenol; indentical placebo

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Age ≥18 years
• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Michelle Ormseth

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michelle J Ormseth, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Central Contacts

Phicharmon Kulapatana (study coordinator)

Role: CONTACT

Phone: 615-936-5747

Email: phicharmon.kulapatana@vumc.org

Facility Contacts

Phicharmon Kulapatana

Role: primary

Other Identifiers

1P01HL174442-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

250944

Identifier Type: -

Identifier Source: org_study_id