2-HOBA for Rheumatoid Arthritis

Overseen By Phicharmon Kulapatana, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: MAO-I, NSAIDs

Disqualifiers: Pregnancy, Cancer, Infection, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 2-HOBA (2-Hydroxybenzylamine, also known as Hobamine) to determine its safety and tolerability for people with rheumatoid arthritis (RA), an autoimmune disease that causes swollen and painful joints. Participants will take either 2-HOBA or a placebo (a look-alike pill with no active ingredients) for four weeks. The trial aims to compare the effects of 2-HOBA on inflammation markers and blood pressure against the placebo. The study seeks individuals with RA who have at least four tender or swollen joints and have not changed certain medications in the past four weeks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that 2-HOBA is likely to be safe for humans?

Research has shown that 2-HOBA is generally safe and well-tolerated. In animal studies, it reduced inflammation and other health issues without causing major side effects. Evidence also indicates that it is safe as a dietary supplement in healthy people, suggesting that the treatment is likely safe for humans. However, specific information about side effects in this trial is not yet available. As this is a phase 2 study, researchers are still carefully monitoring its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for RA?

Most treatments for rheumatoid arthritis, like methotrexate or biologics, work by suppressing the immune system to reduce inflammation. But 2-HOBA, or 2-Hydroxybenzlamine acetate, works differently by targeting oxidative stress, which is a contributor to inflammation. Researchers are excited because this unique mechanism could potentially offer relief without the broad immune suppression seen in current therapies, potentially minimizing side effects. Plus, 2-HOBA is taken orally, making it an easy addition to daily routines.

What evidence suggests that 2-HOBA might be an effective treatment for rheumatoid arthritis?

This trial will compare 2-HOBA with a placebo to evaluate its potential benefits for rheumatoid arthritis. Research has shown that 2-HOBA may reduce inflammation and related issues in animals with autoimmune diseases. It targets harmful compounds called isoLGs, which can increase inflammation. Studies have found that 2-HOBA effectively neutralizes the toxic effects of these isoLGs. Previous research also indicates that 2-HOBA is well-tolerated with few side effects. Although human data remains limited, these early findings suggest it could benefit people with rheumatoid arthritis. ^{2 3 6 7 8}

Who Is on the Research Team?

Michelle J Ormseth, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 2-HOBA
• Placebo

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. reporter.nih.gov reporter.nih.gov/search/Jho8dkcTnEuFXWcmJkslGA/project-details/10825562

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis Aim 2 will compare changes in cellular and plasma isoLG-adducts, markers of inflammation, DAS28 score, and 24-hour blood pressure in active and placebo arms.

2. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT05274243

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10025056/

Inflammation Biomarker Response to Oral 2- ... The use of 2-HOBA, which has been shown to be highly tolerable and relatively no toxicity, efficiently eliminates the toxic effects of IsoLGs ...

4. clinicaltrial.be clinicaltrial.be/en/details/31572?per_page=100&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis - C... In animal models of autoimmunity, hypertension, and atherosclerosis 2-HOBA reduced inflammation, autoantibodies, blood pressure, and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04941599

2-Hydroxybenzylamine (2-HOBA) to Reduce HDL ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

6. clinicaltrial.be clinicaltrial.be/en/details/31572?only_active=0&only_eligible=0&only_recruiting=0&per_page=100

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis - C... Safety/Tolerability (adverse events). Rates of adverse events will be compared between active and placebo arms and presented as summary ...

7. reporter.nih.gov reporter.nih.gov/search/-pm6ufRB0kqVRo9p8eJTrw/project-details/10825562

2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis We propose a phase 2 study to determine 2-HOBA's tolerability, safety, and effect on isoLG- adducts, inflammation and blood pressure in RA patients. Twenty- ...

8. link.springer.com link.springer.com/article/10.1007/s10753-023-01801-w

Inflammation Biomarker Response to Oral 2- ... Given that 2-HOBA has a proven high safety margin, then its use as a nutritional supplement in healthy individuals has a high likelihood of ...