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2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05274243
Recruitment Status : Recruiting
First Posted : March 10, 2022
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
Michelle Ormseth, Vanderbilt University Medical Center

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: 2-HOBA Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 2-HOBA Phase 2 Clinical Trial in Rheumatoid Arthritis
Actual Study Start Date : August 9, 2022
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 2-HOBA
2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day for 4 weeks
Drug: 2-HOBA
2-HOBA acetate (2-Hydroxybenzlamine acetate) 750mg (provided as three 250mg capsules) three times per day for 4 weeks
Other Names:
  • 2-hydroxybenzylamine
  • salicylamine
  • IUPAC name: 2-(aminomethyl)phenol

Placebo Comparator: Placebo
Matching placebo (provided as three capsules) three times per day for 4 weeks
Other: Placebo
Placebo (provided as three capsules) three times a day for 4 weeks




Primary Outcome Measures :
  1. Safety/Tolerability (adverse events) [ Time Frame: Baseline to 4 weeks ]
    Rates of adverse events will be compared between active and placebo arms and presented as summary statistics.

  2. Cellular isolevuglandin (isoLG) adducts [ Time Frame: Baseline to 4 weeks ]
    Change in percentage of cellular isoLG adducts will be compared between active and placebo arms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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, corticosteroids 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05274243


Contacts
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Contact: Annette M Oeser, BS, MLAS 615-322-3778 annette.oeser@vumc.org
Contact: Michelle J Ormseth, MD, MSCI 615-322-4746 Michelle.ormseth@vumc.org

Locations
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United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Annette M Oeser, BS, MLAS    615-322-3778    annette.oeser@vumc.org   
Contact: Michelle J Ormseth, MD, MSCI    615-322-4746    michelle.ormseth@vumc.org   
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Michelle Ormseth, MD, MSCI Vanderbilt University Medical Center
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Responsible Party: Michelle Ormseth, Assistant Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT05274243    
Other Study ID Numbers: 220141
First Posted: March 10, 2022    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Only deidentified data will be available upon reasonable written request in conjunction with appropriate data use agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Starting 6 months after publication and for 1 year.
Access Criteria: Only deidentified data will be available upon reasonable written request in conjunction with appropriate data use agreement. Interested parties may contact the study PI.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michelle Ormseth, Vanderbilt University Medical Center:
Rheumatoid Arthritis
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Phenol
Anti-Infective Agents, Local
Anti-Infective Agents
Disinfectants
Sclerosing Solutions
Pharmaceutical Solutions