Treatment of Early RA: Minocycline in Combination With Methotrexate vs Methotrexate Alone

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 Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Combination of Minocycline and MTX or MTX alone; Drug: methotrexate

Detailed Description

The purpose of this study is to determine if a combination of methotrexate and minocycline works better than methotrexate alone in early Rheumatoid Arthritis (RA). Specific aims of this study are:

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.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Unversity of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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; Other Names: Rheumatrex®; Trexall®; Dynacin®; Minocin®; Myrac®
Active Comparator: 2 Methotrexate; 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.	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.; Other Names: Rheumatrex®; Trexall®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission evaluated by American College of Rheumatology (ACR) outcome variables	Patients will be evaluated and then at 2-month intervals to 12 months using the ACR core set of outcome variables (50) for remission. Additionally hand x-rays will be done.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of combination therapy versus methotrexate alone, Composite Index	Clinically relevant comparison of the effectiveness of combination therapy versus methotrexate alone will be improvement by 20% and/or 70% by the American College of Rheumatology composite index.	48 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2001
• Primary Completion (Actual): May 31, 2006
• Study Completion (Actual): May 31, 2006

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimated): December 24, 2007

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Minocycline
• Other Study ID Numbers: 0519-00 FB

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.: Yes