Study of Methotrexate in Lupus Erythematosus (SMILE)

This study has been completed.
Sponsor:
Collaborator:
McGill University Health Center
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00470522
First received: May 2, 2007
Last updated: May 4, 2007
Last verified: May 2007
  Purpose

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 Intervention Phase
Systemic Lupus Erythematosus
Drug: Methotrexate and folic acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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.

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

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

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

Enrollment: 86
Study Start Date: June 1995
Study Completion Date: December 2001
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470522

Locations
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5T 2S8
Sponsors and Collaborators
University Health Network, Toronto
McGill University Health Center
Investigators
Principal Investigator: Paul R. Fortin, MD University Health Network, Toronto
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00470522     History of Changes
Other Study ID Numbers: TAS Grant 95072
Study First Received: May 2, 2007
Last Updated: May 4, 2007
Health Authority: Canada: Health Canada

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

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

ClinicalTrials.gov processed this record on August 01, 2014