2-HOBA for Rheumatoid Arthritis

Overseen by Michelle J Ormseth, MD, MSCI

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: MAO-I, NSAIDs

Disqualifiers: Pregnancy, Cancer, Infection, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called 2-HOBA for people with rheumatoid arthritis. 2-HOBA helps to clean up harmful chemicals produced by stress in the body, which can cause inflammation and damage. The goal is to see if this treatment is safe and effective in reducing inflammation and heart disease risk in these patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. If you are using non-steroidal anti-inflammatory drugs (NSAIDs), you must stop them for 2 weeks before and during the study. There should be no changes in DMARDs or glucocorticoids for at least 4 weeks before the study.

How is the drug 2-HOBA different from other treatments for rheumatoid arthritis?

2-HOBA (2-Hydroxybenzylamine, Hobamine) is unique because it may target oxidative stress, a different mechanism compared to traditional treatments like methotrexate, which primarily suppresses the immune system. This novel approach could offer an alternative for patients who do not respond well to existing therapies. ^{1 2 3 4 5}

Research Team

Michelle J Ormseth, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

Adults diagnosed with Rheumatoid Arthritis who meet specific criteria and haven't changed their arthritis medications in the last 4 weeks can join. They must not have other autoimmune diseases, recent major surgery, active cancer (except certain skin cancers), or serious infections. Participants should not be pregnant, breastfeeding, or have severe liver/kidney issues.

Inclusion Criteria

I haven't changed my arthritis medication in the last 4 weeks.

Written informed consent

If of childbearing potential, willingness to use effective birth control throughout study and 4 weeks after completion of the study (examples: condom, diaphragm, oral contraceptive pill, intrauterine device)

Exclusion Criteria

Aspirin allergy

I currently have an infection.

I have not had major surgery in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either 750mg 2-HOBA or matching placebo three times a day for 4 weeks

4 weeks

2 visits (in-person at week 0 and week 4)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 2-HOBA (Other)
• Placebo (Other)

Trial Overview The trial is testing the safety and effects of a compound called 2-HOBA (750mg taken three times daily) versus a placebo over four weeks on patients with rheumatoid arthritis. It will measure changes in inflammation markers and disease activity.

Participant Groups

Group I: 2-HOBA Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Matching placebo (provided as three capsules) three times per day for 4 weeks

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Findings from Research

In a study using a murine model of rheumatoid arthritis, carbon monoxide (CO) treatment significantly reduced inflammation and bone erosion compared to untreated controls, highlighting its potential as a therapeutic agent.

Both CO and biliverdin improved clinical disease activity and prevented cartilage degradation, suggesting that these heme degradation products may offer beneficial effects in managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis. Bonelli, M., Savitskaya, A., Steiner, CW., et al.[2017]

Chebulanin, a natural polyphenol from Terminalia chebula, significantly reduced the severity of rheumatoid arthritis in a collagen-induced arthritis mouse model by lowering inflammation markers like IL-6 and TNF-α, and decreasing joint damage.

The study revealed that chebulanin works by inhibiting key signaling pathways (NF-κB and MAPK), which are involved in inflammation, suggesting it could be a promising therapeutic option for managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chebulanin exerts its anti-inflammatory and anti-arthritic effects via inhibiting NF-κB and MAPK activation in collagen-induced arthritis mice. Liu, F., Liu, Y., Zhan, S., et al.[2021]

In a 24-week randomized controlled trial involving 100 patients, Yishen Tongbi decoction (YSTB) was found to be non-inferior to methotrexate (MTX) in reducing disease activity in rheumatoid arthritis, with 67.4% of YSTB patients achieving a clinical disease activity index (CDAI) response compared to 57.1% for MTX.

Both treatments showed similar safety profiles, with no significant difference in drug-related adverse events, suggesting that YSTB could be a viable alternative to MTX for RA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Yishen Tongbi decoction versus methotrexate in patients with active rheumatoid arthritis: A double-blind, randomized, controlled, non-inferiority trial. Xu, J., Zhang, L., Xu, Y., et al.[2023]

The study found that there are more heme oxygenase (HO)-1 expressing cells in the synovium of rheumatoid arthritis (RA) patients compared to those with osteoarthritis (OA), suggesting a potential role of HO-1 in RA pathology.

In RA synovium, cells co-expressing HO-1 and the IgG-Fc/HLA-DR complex were identified, indicating that these cells may function as antigen-presenting cells and could be involved in the production of rheumatoid factor (RF), a key marker in RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of HO-1 expressing synovial lining cells between RA and OA. Yang, S., Ohe, R., Aung, NY., et al.[2021]

Leonurine (LE) significantly reduced joint swelling, bone damage, and inflammation in mice with collagen-induced arthritis, indicating its potential as an effective treatment for rheumatoid arthritis (RA).

LE's therapeutic effects are mediated through the miR-21/YOD1/YAP axis, which regulates the Hippo signaling pathway, leading to decreased proliferation and inflammation of RA-fibroblast-like synoviocytes (FLSs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leonurine alleviates rheumatoid arthritis by regulating the Hippo signaling pathway. Ma, XN., Feng, W., Li, N., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis. [2017]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Chebulanin exerts its anti-inflammatory and anti-arthritic effects via inhibiting NF-κB and MAPK activation in collagen-induced arthritis mice. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of Yishen Tongbi decoction versus methotrexate in patients with active rheumatoid arthritis: A double-blind, randomized, controlled, non-inferiority trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Comparative study of HO-1 expressing synovial lining cells between RA and OA. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Leonurine alleviates rheumatoid arthritis by regulating the Hippo signaling pathway. [2023]