Prediction of Methotrexate Response - A Pilot Study

NCT ID: NCT01726959

Last Updated: 2022-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 36 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-12-31

Brief Summary

The objective of this study is to identify genetic predictors of individual methotrexate (MTX) response in patients with rheumatic diseases by determining genetic and metabolomic factors related to nutrient metabolism and drug transport.

The development of better genetic predictors of individual MTX treatment response would provide invaluable prognostic information prior to initiating treatment, which would allow more appropriate choice of therapy, decreased adverse events, and more efficient dose-escalation of the drug, with ultimate benefits of improved effectiveness and tolerability rates in patients being treated with MTX for autoimmune diseases.

Despite being the gold-standard therapy for rheumatoid arthritis and other types of chronic autoimmune diseases since 1951, MTX's efficacy and safety profile limit its use: MTX is discontinued in greater than 50% of patients secondary to inefficacy or poor tolerability. Upon initial treatment, discontinuation rates approach 12% because of drug toxicity, despite prophylactic measures such as the co-administration of folic acid. The causes of primary failure, secondary failure, and adverse events of MTX may be related to genetic variation of dihydrofolate reductase (DHFR) and other genes involved in folate metabolism, one-carbon transfer, and drug transport. The purpose of this study is to identify genetic variations involved in methotrexate response so that we may better understand the pharmacodynamics of MTX metabolism in patients with rheumatic diseases.

Conditions

Rheumatoid Arthritis; Rheumatic Diseases

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Methotrexate

Methotrexate for rheumatic diseases, 2.5 - 25 mg weekly

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• All adult patients (i.e. >18 years of age) who are enrolled at NorthEast Rheumatology at the Carolinas Medical Center - NorthEast who will be initiating MTX as standard treatment for their particular rheumatic disease, which may include (but not be limited to) conditions such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory-bowel disease related arthropathies, lupus (systemic lupus erythematosus, cutaneous lupus erythematosus), Sjogren's syndrome, Behcet's disease, systemic sclerosis, and vasculitides.
• No prior enrollment into this study
• Enrollment and initial blood sample collection prior to first MTX administration
• Written informed consent

Exclusion Criteria

• NONE

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gordon K. Lam, MD

Role: PRINCIPAL_INVESTIGATOR

Carolinas Medical Center - NorthEast Rheumatology

Locations

Carolinas Medical Center - NorthEast

Concord, North Carolina, United States

Countries

United States

Other Identifiers

MRS1

Identifier Type: -

Identifier Source: org_study_id