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

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

Detailed Description
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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.

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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Combination of Minocycline and MTX or MTX alone
* Drug: methotrexate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Methotrexate* & minocycline<br>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<br>* 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<br>* Other names: Myrac®;|
| Active Comparator: 2 Methotrexate<br>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<br>* 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.<br>* Other names: Trexall®;|

What is the study measuring?
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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 |