Prediction of Methotrexate Response - A Pilot Study

Rheumatoid Arthritis Clinical Trial

— MRS  

Official title:

Prediction of Methotrexate Response - A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01726959
• Other study ID #: MRS1
• Status: Completed
• Start date: December 2011
• Est. completion date: December 2014

Study information

• Verified date: August 2015
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Collagen Diseases
• Rheumatic Diseases
• Rheumatoid Arthritis

Locations

Country	Name	City	State
United States	Carolinas Medical Center - NorthEast	Concord	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lymphocyte proliferation		9 days in culture
Secondary	dihydrofolate reductase expression		9 days in culture