Treatment of Early RA: Minocycline in Combination With Methotrexate vs Methotrexate Alone - Full Text View

Sponsored by:	University of Nebraska
Information provided by:	University of Nebraska
ClinicalTrials.gov Identifier:	NCT00579644

Purpose

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

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: Combination of Minocycline and MTX or MTX alone Drug: methotrexate	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Treatment of Early Rheumatoid Arthritis: Minocycline in Combination With Methotrexate Versus Methotrexate Alone

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Methotrexate Minocycline Minocycline hydrochloride

U.S. FDA Resources

Further study details as provided by University of Nebraska:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	January 2001
Study Completion Date:	May 2006

Arms	Assigned Interventions
1 Methotrexate* & minocycline: Active Comparator 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
2: Active Comparator 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.

Arms

Assigned Interventions

1 Methotrexate* & minocycline: Active Comparator

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

2: Active Comparator

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.

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.

Eligibility

Ages Eligible for Study:	19 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00579644

Sponsors and Collaborators

University of Nebraska

Investigators

Principal Investigator:

James R O'Dell, MD

University of Nebraska

More Information

No publications provided

Responsible Party:	University of Nebraska Medical Center ( James O'Dell, MD Principal Investigator )
Study ID Numbers:	IRB # 519-00 FB
Study First Received:	December 18, 2007
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00579644 History of Changes
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Prednisone
Minocycline
Autoimmune Diseases
Immunologic Factors
Joint Diseases
Arthritis, Rheumatoid
Folate
Rheumatic Diseases
Folinic Acid

Folic Acid Antagonists
Immunosuppressive Agents
Vitamin B9
Folic Acid
Anti-Bacterial Agents
Musculoskeletal Diseases
Arthritis
Connective Tissue Diseases
Methotrexate
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Minocycline
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Arthritis, Rheumatoid
Reproductive Control Agents
Anti-Bacterial Agents
Musculoskeletal Diseases
Arthritis
Therapeutic Uses
Abortifacient Agents

Connective Tissue Diseases
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Autoimmune Diseases
Immune System Diseases
Joint Diseases
Enzyme Inhibitors
Rheumatic Diseases
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 10, 2009