Official Title: “Treatment of Early Rheumatoid Arthritis: Minocycline in Combination With Methotrexate Versus Methotrexate Alone”

The purpose of this study is to determine if a combination of methotrexate and minocycline works better than methotrexate alone in early Rheumatoid Arthritis

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

The purpose of this study is to determine if a combination of methotrexate and minocycline works better than methotrexate alone in early Rheumatoid Arthritis

A. To demonstrate that the combination of minocycline and methotrexate is well tolerated when used in the first year of RA.

B. To compare the efficacy of the combination of minocycline and methotrexate with methotrexate and placebo therapy in early sero-positive RA patients.

Intervention(s) in this Clinical Trial

• Drug: Combination of Minocycline and MTX or MTX alone
  • Methotrexate Dosing: 1)initial dose of methotrexate for all patients will be 10 mg/week. 2)2 month: dose of MTX will remain at 10 mg/week if full remission criteria are met; otherwise, increased to 15 mg/week. 3)4 month: dose of MTX will remain at its current level if full remission criteria are met; otherwise, be increased to 20 mg/week. 4)6, 8 and 10 month: If the patient has fallen below full remission criteria and is not already receiving the maximum dose of 20 mg/week,dose will be increased to 20 mg/week. If the patient meets ACR 50 criteria prednisone will be tapered by 1mg/month 5)12 month evaluation: End of the blinded portion of the study. minocycline dosage 200 mg
• Drug: methotrexate
  • Initial evaluation: The dose of methotrexate for all patients will be 10 mg/week. 2 month evaluation: The dose of MTX will remain at 10 mg/week if full remission criteria are met; otherwise, it will be increased to 15 mg/week. 4 month evaluation: The dose of MTX will remain at its current level if full remission criteria are met; otherwise, it will be increased to 20 mg/week. 6, 8 and 10 month evaluations: If the patient has fallen below full remission criteria and is not already receiving the maximum dose of 20 mg/week, the dose will be increased to 20 mg/week. If the patient meets ACR 50 criteria prednisone will be tapered by 1mg/month 12 month evaluation: End of the blinded portion of the study.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1 Methotrexate* & minocycline
  • Methotrexate Dosing: 1)initial dose of methotrexate for all patients will be 10 mg/week. 2)2 month: dose of MTX will remain at 10 mg/week if full remission criteria are met; otherwise, increased to 15 mg/week. 3)4 month: dose of MTX will remain at its current level if full remission criteria are met; otherwise, be increased to 20 mg/week. 4)6, 8 and 10 month: If the patient has fallen below full remission criteria and is not already receiving the maximum dose of 20 mg/week,dose will be increased to 20 mg/week. If the patient meets ACR 50 criteria prednisone will be tapered by 1mg/month 5)12 month evaluation: End of the blinded portion of the study. minocycline dosage 200 mg
• Active Comparator: 2
  • Methotrexate Dosing: Initial evaluation: The dose of methotrexate for all patients will be 10 mg/week. 2 month evaluation: The dose of MTX will remain at 10 mg/week if full remission criteria are met; otherwise, it will be increased to 15 mg/week. 4 month evaluation: The dose of MTX will remain at its current level if full remission criteria are met; otherwise, it will be increased to 20 mg/week. 6, 8 and 10 month evaluations: If the patient has fallen below full remission criteria and is not already receiving the maximum dose of 20 mg/week, the dose will be increased to 20 mg/week. If the patient meets ACR 50 criteria prednisone will be tapered by 1mg/month 12 month evaluation: End of the blinded portion of the study.

Primary Measures

• Patients will be evaluated and then at 2-month intervals to 12 months using the ACR core sent of outcome variables (50) as detailed in Appendix II, Part A. Additionally hand x-rays will be done.
  • Time Frame: 48 weeks
    Safety Issue?: Yes

Secondary Measures

• Another clinically relevant comparison of the effectiveness of combination therapy versus methotrexate alone will be improvement by 20% and/or 70% by the ACR composite index.
  • Time Frame: 48 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Age over or equal to 19 years old and less than or equal to 75 years old
• Diagnosis of RA as determined by fulfilling 4 of 7 ACR criteria
• Positive rheumatoid factor
• Duration of disease: greater than six weeks and less than one year

Exclusion Criteria:

• Allergy to tetracycline or methotrexate
• Previous DMARD treatment
• Doses of oral steroids greater than 7.5 mg/day
• Intra-articular injections within the last four weeks
• Significant liver or renal disease or active peptic ulcer disease
• Patients who are not willing to abstain from alcohol consumption
• Women of childbearing potential who are not practicing a successful method of contraception

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Nebraska

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00579644

Study ID Number: IRB # 519-00 FB

ClinicalTrials.gov Identifier: NCT00579644

Health Authority: United States: Institutional Review Board