2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05274243
• Other study ID #: 220141
• Status: Recruiting
• Phase: Phase 2
• Start date: August 9, 2022
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: Annette M Oeser, BS, MLAS
• Phone: 615-322-3778
• Email: annette.oeser[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• 2-HOBA
2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day for 4 weeks

Other:
• Placebo
Placebo (provided as three capsules) three times a day for 4 weeks

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/Tolerability (adverse events)	Rates of adverse events will be compared between active and placebo arms and presented as summary statistics.	Baseline to 4 weeks
Primary	Cellular isolevuglandin (isoLG) adducts	Change in percentage of cellular isoLG adducts will be compared between active and placebo arms.	Baseline to 4 weeks