Prediction of Methotrexate Response - A Pilot Study (MRS)

August 31, 2022 updated by: Wake Forest University Health Sciences

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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Concord, North Carolina, United States, 28025
        • Carolinas Medical Center - Northeast

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Methotrexate
Methotrexate for rheumatic diseases, 2.5 - 25 mg weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
lymphocyte proliferation
Time Frame: 9 days in culture
9 days in culture

Secondary Outcome Measures

Outcome Measure
Time Frame
dihydrofolate reductase expression
Time Frame: 9 days in culture
9 days in culture

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

University of North Carolina, Chapel Hill

Investigators

  • Principal Investigator: Gordon K. Lam, MD, Carolinas Medical Center - NorthEast Rheumatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (ACTUAL)

December 1, 2014

Study Completion (ACTUAL)

December 1, 2014

Study Registration Dates

First Submitted

November 12, 2012

First Submitted That Met QC Criteria

November 14, 2012

First Posted (ESTIMATE)

November 15, 2012

Study Record Updates

Last Update Posted (ACTUAL)

September 2, 2022

Last Update Submitted That Met QC Criteria

August 31, 2022

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MRS1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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