Study of Methotrexate in Lupus Erythematosus (SMILE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00470522
Recruitment Status : Completed
First Posted : May 7, 2007
Last Update Posted : May 7, 2007
McGill University Health Center
Information provided by:
University Health Network, Toronto

Brief Summary:
The treatment of systemic lupus erythematosus (SLE) has been aimed at decreasing mortality and morbidity because the etiology of the disease is unknown. The general aim of this multicentre randomized placebo-controlled trial of low dose intermittent methotrexate with folic acid is to establish whether methotrexate shows efficacy and safety in controlling disease activity in SLE and preventing flares in disease activity or development of end-organ damage. A second aim will be to document the steroid sparing effect of methotrexate in SLE. A Third aim will be to measure toxicity and utility of methotrexate with folic acid and to perform effectiveness and utility analyses.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Methotrexate and folic acid Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A Canadian Multicenter, Randomized, Double-Blind Placebo-Controlled Study of Methotrexate and Folic Acid in Systemic Lupus Erythematosus: A Phase III Trial.
Study Start Date : June 1995
Actual Study Completion Date : December 2001

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. SLAM - Systemic Lupus Activity Measure [ Time Frame: at one year ]
  2. Daily dose of prednisone [ Time Frame: at one year ]

Secondary Outcome Measures :
  1. SLICC DI - Systemic Lupus International Collaborating Clinic Damage Index [ Time Frame: at one year ]
  2. SF-36 - Short Form 36 [ Time Frame: at one year ]
  3. SLEDAI - Systemic Lupus Erythematosus Disease Activity Index [ Time Frame: at one year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • men and women with diagnosis of SLE
  • 18 years and above
  • negative pregnancy test for female subjects of child-bearing age and must accept not to attempt to get pregnant during the period of the study
  • Subject with active disease as defined by SLAM of at least 8
  • SLICC/ACR damage index of less or equal to 15
  • Subject must be on stable does of NSAIDs, prednisone, or antimalarial (chloroquine sulfate or hydroxychloroquine) at least 4 weeks preceding the study
  • subjects can be under other medications as long as condition or treatment will not interfere with the experimental medications and assessments
  • must understand either French or English and can give written informed consent

Exclusion Criteria:

  • previous history of hypersensitivity or intolerance to methotrexate or folic acid
  • total SLAM of less than 8 or total SLICC/ACR score of more than 15.
  • history of medical non-compliance or inability to comply with instructions
  • subject who have received intra-articular or intramuscular corticosteroids in the four weeks prior to study entry.
  • clinically significant acute or chronic liver disease with the exception of autoimmune liver disease
  • alcohol use in excess of 2 ounces of 100 proof liquor or its equivalent/week
  • insulin requiring diabetes mellitus with morbid obesity
  • renal impairment such that the serum creatinine is more than or equal to 175 umol/I (SI units) or 2.0 mg/dl
  • interstitial lung disease as defined by an abnormal chest x-ray or decrease diffusion capacity (DLCO < 70% of predicted) without evidence of pulmonary hypertension.
  • WBC count ,3,000/ cubic mm. and/or platelet count ,80,000/ cubic mm.
  • prior use of methotrexate to treat SLE
  • use of sulfa drugs that may potentiate the folate antagonistic effects of MTX
  • non-steroidal anti-inflammatory drugs will be allowed throughout the trial unless there is evidence of renal failure or other contra-indications to these drugs. Their con-comitant use with MTX is routine in patients with rheumatoid arthritis.
  • use of another cytotoxic or immunosuppressive drug such as cyclophosphamide, azathioprine, chlorambucil, cyclosporin or trimetoprime currently or in the preceding 6 months.
  • current participation in any other drug trial or participation in such a trial in the previous one month.
  • serologic evidence of infection with HIV
  • biologic potential for pregnancy and not utilizing effective means of contraception
  • recently (less than 6 months) diagnosed malignancy
  • vitamin B12 deficiency

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00470522

Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5T 2S8
Sponsors and Collaborators
University Health Network, Toronto
McGill University Health Center
Principal Investigator: Paul R. Fortin, MD University Health Network, Toronto Identifier: NCT00470522     History of Changes
Other Study ID Numbers: TAS Grant 95072
First Posted: May 7, 2007    Key Record Dates
Last Update Posted: May 7, 2007
Last Verified: May 2007

Keywords provided by University Health Network, Toronto:
folic acid
systemic lupus erythematosus

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Folic Acid
Vitamin B Complex
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Growth Substances