Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis
Brief summary
This is a phase 2 study to determine 2-HOBA's tolerability, safety, and effect on isoLG-adducts in patients with rheumatoid arthritis (RA) patients. Up to 32 subjects will be randomized to 750mg 2-HOBA or matching placebo three times a day for 4 weeks. As primary outcome measures investigators will compare tolerability and adverse events and changes in isoLG adducts in active and placebo arms. Among prespecified exploratory outcomes investigators will compare changes in markers of inflammation, DAS28 score, and 24-hour blood pressure in active and placebo arms. This pilot study will inform the feasibility and design of future studies to examine the efficacy of 2-HOBA in RA patients.
Detailed description
Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease affecting 1% of the population. Aggressive treatment is a fundamental therapeutic strategy to improve disease-related outcomes and cardiovascular disease, which contributes to excess mortality in RA. Thus, therapeutics targeting novel pathways that treat RA and reduce cardiovascular risk are needed. A potential target is blocking the proinflammatory, immunogenic, and proatherogenic consequences of isolevuglandins (isoLGs). 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 autoimmunity, hypertension, and atherosclerosis 2-HOBA reduced inflammation, autoantibodies, blood pressure, and atherosclerosis, and in human phase 1 clinical studies in healthy volunteers 2-HOBA was well tolerated. In this phase 2 study investigators will randomize up to 32 subjects with RA meeting inclusion/exclusion criteria to 750mg 2-HOBA or matching placebo three times a day for 4 weeks. Randomized subjects will have study visits at week 0 and week 4. At each visit a history and physical exam with joint counts, questionnaire, blood draw and 24-hour blood pressure will be performed.
Interventions
DRUG2-HOBA
2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day for 4 weeks
OTHERPlacebo
Placebo (provided as three capsules) three times a day for 4 weeks
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Age ≥18 years * Meets 2010 American College of Rheumatology/European League Against Rheumatism Rheumatoid Arthritis classification criteria * ≥ 4 tender or swollen joints * No change in DMARDs, glucocorticoids in ≥ 4 weeks * If of childbearing potential, willingness to use effective birth throughout study and 4 weeks after completion of the study (examples: condom, diaphragm, oral contraceptive pill, intrauterine device) * If using non-steroidal anti-inflammatory drugs (NSAIDs), willingness to discontinue use of NSAIDs for 2 weeks prior to the study and throughout the study
Exclusion criteria
* Pregnant or breastfeeding * Active cancer except non-melanoma skin cancer * Active infection * Concomitant inflammatory autoimmune disease * Major surgery in ≤ 3 months * Aspirin allergy * Use of MAO-I * Estimated creatinine clearance \<30 ml/min * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety/Tolerability (Adverse Events) | Baseline to 4 weeks | Rates of adverse events will be compared between active and placebo arms and presented as summary statistics. Number of participants having an adverse event are reported. |
| Cellular Isolevuglandin (isoLG) Adducts | Baseline to 4 weeks | Change in percentage of cellular isoLG adducts will be compared between active and placebo arms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichelle Ormseth, MD, MSCI
Vanderbilt University Medical Center
Participant flow
Recruitment details
43 patients were screened for eligibility between December 2022 and April 2025 at Vanderbilt University Medical Center.
Pre-assignment details
32 of screen participants were randomized. Of the 11 not randomized, 9 did not meet inclusion criteria and 2 were unable to be recontacted.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 14 |
| other Total, other adverse events | 9 / 16 | 9 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
None listed