Prediction of Methotrexate Response - A Pilot Study

NCT01726959 | Completed

• 1 other identifier: MRS1
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

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

Keywords

methotrexate

Outcome Measures

Primary Outcomes (1)

• lymphocyte proliferation

  9 days in culture

Secondary Outcomes (1)

• dihydrofolate reductase expression

  9 days in culture

Study Arms (1)

Methotrexate

Methotrexate for rheumatic diseases, 2.5 - 25 mg weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with rheumatic disease being newly treated with methotrexate, recruited from a single rheumatology practice

You may qualify if:

• 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

You may not qualify if:

• NONE

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• University of North Carolina, Chapel Hill: collaborator

Study Sites (1)

Carolinas Medical Center - NorthEast

Concord, North Carolina, 28025, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Rheumatic Diseases

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Gordon K. Lam, MD

  Carolinas Medical Center - NorthEast Rheumatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 15, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 2, 2022

Record last verified: 2015-08

Locations

US (1)