Comparison of the Tuberculin Skin Test (TST) and QuantiFERON ®-TB Gold Test (QFT-G) In Patients With Rheumatoid Arthritis Being Considered for Anti-TNF-Alpha Therapy

December 11, 2009 updated by: Walter Reed Army Medical Center
This research will help doctors interested in the usefulness of a new test to discover hidden tuberculosis infections in patients diagnosed with rheumatoid arthritis (RA). This new test is called Quantiferon-Gold (QFT-G). After immune system medicines that block TNF-alpha (a protein manufactured by white blood cells to stimulate and activate the immune system in response to infection or cancer) started to be used, the rate of tuberculosis infections in patients treated with these medicines has increased. Doctors think that the investigators may be missing some tuberculosis infections that were hidden before the medicine is started. This new QFT-G test might better diagnose these hidden tuberculosis infections than the current tuberculosis skin test, also known as a PPD/TST. The investigators would like to compare these two tests to find out which is better at detecting these hidden infections. At the same time the investigators will measure the strength of the patient's immune system with a blood test. If you are being considered for a TNF-alpha inhibitor medicine, or are getting the patient's routine PPD/TST, the investigators are asking for the patient's participation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

In recent years the use of biologic agents for the treatment of rheumatic conditions has called into question the utility of the classic tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI). Current clinical rheumatology practice requires potential candidates of biologic therapy to have a negative TST before beginning biologic therapy. But since the TST is time consuming, operator dependent, and fraught with error, it may fail to alert physicians of LTBI in patients with autoimmune diseases and or pharmaceutical immunosuppression. Reactions to intradermal antigen placement requires many cellular interactions, but chiefly they must possess , a sufficient number of memory T cells, the ability to proliferate a clone of T cells specific to the antigen that is introduced, and the ability to traffic these effector cells to the local site. If any of these components are missing the individual may be unable to mount a type IV hypersensitivity (DTH-IV) reaction which is the basis for the TST. While many have recently compared the performance of the new IFN-gamma release assays (IGRAs) like the QuantiFERON-γ TB GOLD® (QFT-G) to the TST for the diagnosis of LTBI, no one has investigated the immunologic factors that may affect these results. Some have postulated that the QFT-G may be less affected by immune-suppression than the TST in patients with rheumatoid arthritis (RA). But recently this was called into question when significant numbers of indeterminate QFT-G results were seen in RA patients. Therefore, we plan to address two current clinical questions. First, what is the best screening strategy for LTBI in RA patients being started on biologic agents - TST, QFT-G or both? Second, is there utility in conducting immune competence testing in RA patients to predict those whom may be unable to generate a positive TST and/or QFT-G. This observational and exploratory pilot study will compare normal matched controls to RA patients being considered for anti-TNF alpha therapy. We will perform a comprehensive evaluation of the immune system by measuring memory T cell numbers with flow cytometry, the ability of memory T cells to proliferate to the tuberculin antigen or purified protein derivative (PPD), and phytohemagglutinin (PHA) antigen via the lymphocyte proliferation assay QunatiFERON-CMI.™ We will also investigate memory T cell trafficking ability via intradermal PPD and PHA antigen placement. Results of QFT-G tests will be compared to the TST with an emphasis on those results which are discordant. We will further attempt to identify immunocompetence testing which may help identify those patients who are unable to mount a DTH-IV response. In order to detect a statistical difference in this specific test population we will use analysis of variance for continuous or ordinal variables and the chi-square test (or Fisher exact test) for categorical data statistics. We hope to contribute to the body of literature regarding the best screening strategy for LTBI in patients with RA, and explore the concept of screening for immune competence in this specific population, which has not been elucidated in the literature.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20307
        • Recruiting
        • Walter Reed Army Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Adam T Armstrong, DO
        • Principal Investigator:
          • Robert O Holmes, DO

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

patients in the US government tricare health system

Description

Inclusion Criteria:

Study group:

  • Any patient 18 years or older who has been diagnosed with RA (American College of Rheumatology (ACR) criteria) and is being considered for de novo anti-TNF alpha therapy will be invited to participate in this study.

Control group:

  • Control subjects will be any patient 18 years or older presenting to the Allergy/Immunology clinic for routine TST.

Exclusion Criteria:

Study group:

  • We will exclude any individual with a previous history of known immuno-compromising disease state or unstable medical condition other than RA resulting in overall poor health and/or protein calorie deprivation to include:

    • any other autoimmune disease
    • oral steroid use in the past 3 days (4 half-lives of prednisone is 14 hours)
    • inhaled steroid use at a dose of > 2000 mg beclomethasone equivalent/day
    • any cancer [solid organ or blood]
    • radiation therapy in prior three months
    • any bleeding disorders
    • chemotherapeutic agents
    • transfusion or blood products in past 1 year
    • history of HIV
    • chronic hepatitis
    • malignancy
    • transplant history
    • chronic infection
    • chronic renal failure
    • current allergy treatment (shots, antihistamines)
    • uncontrolled diabetes, or the inability to provide informed consent
    • we will also exclude individuals with immediate hypersensitivity to the TST/PPD or PHA antigens
    • a previous severe local ulceration with TST/PPD
    • suspected active TB, previous TB treatment

Control group:

  • We will exclude any individual with known history of anti-TNF alpha therapy.
  • We will also exclude any patient with a history of any immune-modulatory (DMARD) therapy (steroids, anti-TNF agents, methotrexate, azathioprine, sulfasalazine, etc.) within the previous 12 months.
  • Additionally we will exclude all those individuals with previous history of TB or TB therapy, diabetes mellitus, HIV, malignancy, or hepatitis that may influence the dermal reaction to PHA antigen or ex vivo CMI activity.

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

  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
1
The study group will consist of RA patients of the Walter Reed Army Medical Center (WRAMC) rheumatology clinic being considered for treatment with anti-TNF alpha therapy. We will enter patients into the study over a projected course of 12-24 months or until we reach the statistical requirement of 60 subjects.
2
The control group will consist of healthy subjects without known immune-dysregulation or history of treatment with biologic agents who present to the WRAMC Allergy- Immunology clinic for routine screening TST as a part of current WRAMC policy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Primary endpoints are the results of the QFT-G test (defined as positive, negative or indeterminate) and the results of the TST (defined as positive or negative).
Time Frame: Patients will be enrolled over a 2 year time frame
Patients will be enrolled over a 2 year time frame

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Secondary endpoints include the percentage and numbers of CD45RO (memory T cells), the response PHA intradermal antigen placement, numbers of hypoergic TSTs, and the results of cell mediated immunity (CMI) assays.
Time Frame: Patients will be enrolled over a 2 year time period
Patients will be enrolled over a 2 year time period

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Walter Reed Army Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Naval Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Adam T Armstrong, DO, Rheumatology Fellow - Walter Reed Army Medical Center
  • Study Chair: Robert O Holmes, DO, National Naval Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2009

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2011

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 13, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 14, 2009

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2009

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 6950

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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