Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

January 2, 2024 updated by: University of Nebraska
This is a 16-week, open-label study to identify factors that help predict clinical responses to DMARD therapies for RA (Rheumatoid Arthritis) patients. All patients will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a subject becomes intolerant to a DMARD medication the subject will be withdrawn from the study at the discretion of the investigator. Visits (prior to week 16) where withdrawal is determined to be necessary will be considered end of study. End of study data (week 16) as well as study serum will be collected. (Serum only collected on those subjects who have consented to the addendum Serum and DNA of this study). A portion of the blood collected at baseline, week 8 and week 16 with the addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. The radicals have been shown to be associated with inflammation and may correlate with the progression of RA. If this is true, then treatment with RA should decrease the levels of these radicals signaling response to treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of the study is to gather, in a prospective manner, information on patients with rheumatoid arthritis and their response to DMARD therapy. Specific aims of this study are:

A. To evaluate the efficacy of DMARD therapy as defined by attaining ACR 50 response after 16 weeks of therapy.

B. To identify predictors of DMARD response in patients with RA.

  • Does the presence of certain genetic factors such as the shared epitope predict DMARD response
  • Does the presence of serological factors (e.g. ccp (cyclic citrullinated peptide) isotypes) predict DMARD response
  • Does evidence of co-morbid conditions (e.g. periodontal disease) predict DMARD response

A maximum of 400 RA patients will be consented for this protocol. Subject accrual for protocol v1.0 included UNMC (University of Nebraska Medical Center) and the RAIN (Rheumatoid Arthritis Investigational Network) sites. Subject accrual for protocol v2.0 will be derived exclusively from UNMC. Investigators have examined the discriminatory characteristics of several clinical and biologic parameters in predicting treatment response (at least 50% improvement based on ACR criteria) in initial analyses involving 54 participants with early RA treated with methotrexate monotherapy in past RAIN clinical trials. In the initial analyses, factors showing discriminatory characteristics have included rheumatoid factor (RF) isotypes (particularly IgA (Immunoglobulin A) and IgM (Immunoglobulin M), matrix metalloproteinase (MMP)-3, HLA-DRB1 (human leukocyte antigen-DR isotope) shared epitope (SE)-containing alleles, C-reactive protein, and interleukin (IL)-1. For instance, we have found that subjects with low serum concentrations of RF-IgM (< 27 IU/ml) are more likely to be non-responders than those with higher (> 27 IU/ml) serum concentrations (79% vs. 43%).

Males and females will participate in this protocol. As RA is approximately three times more common in females, it is anticipated that a higher percentage of the study subjects will be female. Subjects will be > 19 years of age. This age range was chosen because the age of majority in Nebraska is 19. RA diagnosed before the age of 19 may not have the same disease characteristics as defined by the American College of Rheumatology (ACR) criterion for RA. Pediatric subjects will not be enrolled in this study. Rheumatoid arthritis occurs in all races. No enrollment restrictions have been based on race or ethnic origin.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Principal Investigator:
          • James R O'Dell, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA:

  • Diag. with RA with 4 of 7 ACR criteria: 1) Morning stiffness for at least 1 hr. and at least 6 wks 2) Swelling of 3 or more joints for at least 6 wks. 3) Swelling of wrist, MCP, or proximal interphalangeal joints for 6 or more wks 4) Symmetric joint swelling. 5) Hand x-rays with erosions or bony decalcifications. 6) RA nodules 7) RF positive
  • >19 yrs old at time of diagnosis of RA
  • Current active disease with at least1 swollen joint
  • Starting new DMARD medication(s) please circle: abatacept, adalimumab, azathioprine, barcitinib, certolizumab, etanercept, golimumab, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, rituximab, sarilumab, sulfasalazine, tofacitinib
  • If on other DMARDS, must be on stable dose for ≥ 6 wks
  • If on glucocorticoids must be on stable dose for 2 wks (< 10mg of Prednisone per day or equivalent)
  • Able to adhere to study visit schedule: enrollment, 8 wks & 16 wks (+/- 2 wks)
  • Hgb > 9g/dl
  • WBC > 3.5
  • Neutrophils > 1.0
  • Platelets >100
  • Creatinine <1.6
  • AST or ALT not over 1.2 x upper limit
  • Albumin: up to 1.0 g/dL less than lower limit of normal

EXCLUSION CRITERIA:

  • Pregnant or breastfeeding women
  • Men and women of child bearing potential not willing to practice successful method of contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methotrexate Therapy
Subjects will receive methotrexate therapy for RA treatment.
Drug: Methotrexate
Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg. daily.
Other Names:
  • MTX
Active Comparator: Abatacept Therapy
Subjects will receive abatacept therapy for RA treatment.
Drug: Abatacept
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Orencia
Active Comparator: Adalimumab Therapy
Subjects will receive adalimumab therapy for RA treatment.
Drug: Adalimumab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Humira
Active Comparator: Azathioprine Therapy
Subjects will receive azathioprine therapy for RA treatment.
Drug: Azathioprine
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Imuran
Active Comparator: Barcitinib Therapy
Subjects will receive barcitinib therapy for RA treatment.
Drug: Baricitinib
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Olimuant
Active Comparator: Certolizumab Therapy
Subjects will receive certolizumab therapy for RA treatment.
Drug: Certolizumab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Cimzia
Active Comparator: Etanercept Therapy
Subjects will receive etanercept therapy for RA treatment.
Drug: Etanercept
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Enbrel
Active Comparator: Golimumab Therapy
Subjects will receive golimumab therapy for RA treatment.
Drug: Golimumab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Simponi
Active Comparator: Hydroxycholoroquine Therapy
Subjects will receive hydroxychloroquine therapy for RA treatment.
Drug: Hydroxychloroquine
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Plaquenil
Active Comparator: Infliximab Therapy
Subjects will receive infliximab therapy for RA treatment.
Drug: Infliximab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Remicade
Active Comparator: Leflunomide Therapy
Subjects will receive leflunomide therapy for RA treatment.
Drug: Leflunomide
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Arava
Active Comparator: Minocycline Therapy
Subjects will receive minocycline therapy for RA treatment.
Drug: Minocycline
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Minocin
Active Comparator: Rituximab Therapy
Subjects will receive rituximab therapy for RA treatment.
Drug: Rituximab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Rituxin
Active Comparator: Sarilumab Therapy
Subjects will receive sarilumab therapy for RA treatment.
Drug: Sarilumab
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Kevzara
Active Comparator: Sulfasalazine Therapy
Subjects will receive sulfasalazine therapy for RA treatment.
Drug: Sulfasalazine
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Azulfidine
Active Comparator: Tofacitinib Therapy
Subjects will receive tofacitinib therapy for RA treatment.
Drug: Tofacitinib
Starting dose which may be adjusted as needed at the discretion of the investigator
Other Names:
  • Xeljanz

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of DMARD therapy for Rheumatoid Arthritis as defined by attaining ACR 50 response after 16 weeks of therapy.
Time Frame: 16 weeks
The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks
To identify predictors of DMARD response in patients with RA
Time Frame: 16 weeks
What are predictors of DMARD response in RA patients?
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Using ACR 50 composite measure, does the presence of certain genetic factors such as the shared epitope predict DMARD response
Time Frame: 16 weeks
After 16 weeks of treatment, what is the number of participants with genetic factors such as the shared epitope demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks
Using ACR 50 composite measure, does the presence of serological factors (e.g. CCP isotypes) predict DMARD response
Time Frame: 16 weeks
After 16 weeks of treatment, what is the number of participants with serological factors such as CCP isotypes demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks
Using ACR 50 composite measure, does evidence of co-morbid conditions (e.g. periodontal disease) predict DMARD response
Time Frame: 16 weeks
After 16 weeks of treatment, what is the number of participants with co-morbid conditions such as periodontal disease, demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: James R O'Dell, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2007

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

January 2, 2014

First Submitted That Met QC Criteria

January 22, 2018

First Posted (Actual)

January 30, 2018

Study Record Updates

Last Update Posted (Actual)

January 3, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0439-23-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data remains stored at UNMC for approved investigators at this site only at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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