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IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02451748
Recruitment Status : Completed
First Posted : May 22, 2015
Last Update Posted : July 15, 2020
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Shiva Shahrara, University of Illinois at Chicago

Tracking Information
First Submitted Date  ICMJE May 6, 2015
First Posted Date  ICMJE May 22, 2015
Last Update Posted Date July 15, 2020
Actual Study Start Date  ICMJE August 2015
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
IL-7 and IL-7R expression in peripheral blood mononuclear cells, peripheral blood monocytes or differentiated macrophages of RA patients with active vs. inactive disease treated with DMARD and/or CIMZIA. [ Time Frame: RA subjects treated with (DMARDs) only, blood will only be taken once at the subjects routine visit. An expected average of 4-6 weeks. ]
Expression of IL-7 and IL-7R mRNA was measured in patients that were treated with or without DMARDs in RA patients by real-time RT-PCR.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2015)
IL-7 and IL-7R expression in peripheral blood mononuclear cells, peripheral blood monocytes or differentiated macrophages of RA patients with active vs. inactive disease treated with DMARD and/or CIMZIA. [ Time Frame: RA subjects treated with (DMARDs) only, blood will only be taken once at the subjects routine visit. An expected average of 4-6 weeks. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
IL-7 and IL-7R expression in peripheral blood mononuclear cells, peripheral blood monocytes or differentiated macrophages of RA patients with active vs. inactive disease treated with DMARD and/or CIMZIA. [ Time Frame: The subjects that receive (DMARDs) plus Cimzia, blood samples will be collected onset of the study as well as 3 and 6 months. Peripheral blood mononuclear cells will be isolated from the blood and expression of IL-7 and IL-7R will be determined by real-t ]
Expression of IL-7 and IL-7R mRNA was measured in RA patients that were treated with Certolizumab pegol (Cimzia®) by real-time RT-PCR.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2015)
IL-7 and IL-7R expression in peripheral blood mononuclear cells, peripheral blood monocytes or differentiated macrophages of RA patients with active vs. inactive disease treated with DMARD and/or CIMZIA. [ Time Frame: The subjects that receive (DMARDs) plus Cimzia, blood samples will be collected onset of the study as well as 3 and 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA
Official Title  ICMJE IL-7 and IL-7R Expression in Peripheral Blood Mononuclear Cells, Peripheral Blood Monocytes or Differentiated Macrophages of Rheumatoid Arthritis Patients With Active vs. Inactive Disease Treated With DMARD and/or CIMZIA
Brief Summary The purpose of the study is to better understand the factors present in the cells of inflamed joints of patients with arthritis that may cause rheumatoid arthritis. Knowledge gained from this study may lead to new and better therapies for arthritis.
Detailed Description

Blood samples will be collected from patients that have been diagnosed with RA based on ACR classification criteria. The study will include 200 donors. The total number of subjects are divided into two groups to yield a power of 95% at a type I error 5% level [determined based on the preliminary data]. In the first group, 200 donors will be treated with methotrexate, plaquenil and/or prednisone (Disease modifying anti rheumatic drugs; DMARDs) that either achieve remission (Disease activity score, DAS28<2.6) or do not achieve remission (DAS28>2.6). 50 donor will be utilized as they respond to DMARDs and achieve remission (DAS28<2.6) and 150 donors that do not respond to DMARDs will be transferred to second group. In the second group, 150 donors will be treated with methotrexate, plaquenil and/or prednisone and Cimzia® (provided to us by UCB).

In the first group of patients, blood samples will be obtained from RA patients treated with Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone that achieve remission (DAS28<2.6). The patients that achieve remission (DAS28<2.6), blood will only be taken once at the patients routine visit.

The second group will consist of RA patients that did not respond to "DMARDs". These patients will further receive (DMARDs) such as methotrexate, plaquenil and/or prednisone as well as Cimzia® (provided to us by UCB) free of charge. Cimzia® is a FDA approved drug and is a standard of care. Blood samples will be obtained from the patients treated with DMARDs including methotrexate, plaquenil, and/or prednisone and Cimzia® (provided to us by UCB) that have inactive remission (DAS28<2.6). In this group, blood samples will be collected onset of the study as well as 3 and 6 months after treatment with Cimzia at patient's visit through our collaboration with the aforementioned rheumatologists. Patients receiving intra-articular steroid injections will be excluded from the study.

PB mononuclear cells will be isolated from RA whole blood and drawn into Blood collection tubes and isolated by Histopaque gradient centrifugation. Monocytes will be isolated from RA PB mononuclear cells by negative selection (as shown in the preliminary data) and half of the monocytes will be differentiated to macrophages for 7 days. The expression levels for IL-7 and IL-7R will be determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry analysis.

In our statistical analysis, we will first perform a stratified analysis to evaluate the differential expression levels in RA patients with active and inactive disease, controlling for the type of treatment. Data analysis will be performed in collaboration with an UIC Center for Clinical and Translational Science statistician. Specifically, we will perform the comparison of IL-7 and IL-7R expression among RA patients with active (DAS28>2.6) vs. inactive disease (DAS28<2.6) for DMARDs group (group 1). We will then perform a similar comparison for the DMARDs and Cimzia® therapy group (group 2). The stratified analysis can adjust for the potential confounding effect of treatment received and allows for the detection of the potential differential relationships between expression levels of IL-7 or IL-7R and disease status. We will also perform a pooled regression analysis in which the expression logarithm of IL-7 or IL-7R from patients is regressed on the treatment group indicator [DMARDs (group 1) versus on DMARDs plus Cimzia® therapy (group 2)] and disease status (active or inactive disease) which would demonstrate the interaction between treatment groups and disease activity. Such an analysis pools subjects from two treatment groups together and can therefore increase the sample size, and hence potentially the power of detecting the relationships between biomarkers and disease status. The RA samples will be collected over a 2 year period and the data will be analyzed in the last year of the proposal.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Intervention Model Description:
In this study we determine whether expression of IL-7 and IL-7 receptor (R) is modulated by anti-tumor necrosis factor (TNF) treatment. For this purpose blood is obtained from RA patients prior to anti-TNF (Cimzia treatment; day 0) and after 3 months as well as 6 months of therapy. Transcription levels of IL-7 and IL-7R are examined from the peripheral blood obtained from day 0, 3 and 6 months of therapy. Results of this study will be reported in the MS in preparation.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Other: Lab Work
    Lab work to measure IL-7 and IL-7R
  • Drug: Certolizumab pegol (CDP870, tradename Cimzia)(prefilled syringes at the dose of 200mg)

    Certolizumab pegol (CDP870, tradename Cimzia) or is provided in prefilled syringes at the dose of 200mg.

    Patients received 2x200mg at weeks 0, 2 and 4. Additionally a maintenance dose of 200mg is given every 2 weeks. Treatment is performed through subcutaneous injection.

    Other Name: Certolizumab pegol
  • Drug: Certolizumab pegol (CDP870, tradename Cimzia)

    rtolizumab pegol (CDP870, tradename Cimzia) or is provided in prefilled syringes at the dose of 200mg.

    Patients received 2x200mg at weeks 0, 2 and 4. Additionally a maintenance dose of 200mg is given every 2 weeks. Treatment is performed through subcutaneous injection.

    Other Name: Certolizumab pegol
  • Drug: Hydroxychloroquine
    some patients are on 400mg/day of hydroxychloroquine.
  • Drug: Sulfasalazine
    some patients are on 300 mg/day and some patients are on 1000 mg/day dose of sulfasalazine
  • Drug: Medrol
    some patients are on 8mg/day of medrol
  • Drug: Prednisone
    some patients are on 10mg /day, some patients are on 20 mg/day, some patients are on 2.5 mg/day, some patients are on 30 mg/day, and some patients are on 5 mg/day of prednisone
  • Drug: Triamcinolone
    some patients are on Triamcinolone 40-80mg IM monthly (received 40mg dose 1 week before blood draw, off enbrel 50mg weekly and SSZ 1000mg bid for ~ 3 months) some patients are on Triamcinolone 40mg IM monthly
  • Drug: Naproxen
    some patients are on 1000 mg/day of naproxen
  • Drug: Leflunomide
    some patients are on 20mg/day of leflunomide
  • Drug: Methotrexate
    some patients are on 20mg weekly, some patients are on 25mg weekly, some patients are on 17.5 mg, some patients are on 15 mg weekly, some patients are on 7.5 mg weekly, and some patients are on 15 mg weekly dose of methotrexate
  • Drug: humira
    some patients are on Humira 40mg q2weeks
Study Arms  ICMJE
  • DMARD's Responder and Non-Responder
    In the first group of subjects, blood samples will be obtained from (50) RA subjects with Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone that achieve remission (DAS28<2.6). The subjects that achieve remission (DAS28<2.6), blood will only be taken once at the subjects routine visit. Subject's that are non-responder to DMARDS will go onto group 2.
    Intervention: Other: Lab Work
  • DMARD's plus Cimzia (Certolizumab pegol)
    The second group will consist of (150) RA subjects that did not respond to "DMARDs". These patients will further receive (DMARDs) such as methotrexate, plaquenil and/or prednisone as well as Cimzia®. In this Arm, blood samples will be collected onset of the study as well as 3 and 6 months after treatment with Cimzia at subject's visit through our collaboration with the aforementioned rheumatologists.
    Interventions:
    • Other: Lab Work
    • Drug: Certolizumab pegol (CDP870, tradename Cimzia)(prefilled syringes at the dose of 200mg)
    • Drug: Certolizumab pegol (CDP870, tradename Cimzia)
    • Drug: Hydroxychloroquine
    • Drug: Sulfasalazine
    • Drug: Medrol
    • Drug: Prednisone
    • Drug: Triamcinolone
    • Drug: Naproxen
    • Drug: Leflunomide
    • Drug: Methotrexate
    • Drug: humira
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 7, 2018)
32
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2015)
200
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Must meet 1987 Revised Criteria for the Classification of Rheumatoid Arthritis defined as the diagnosis of the referring physician.
  2. Persistent knee swelling (>ARA grade 2) for 2 weeks, and no recent intra-articular corticosteroid injection.
  3. Age 18 years and older.
  4. Must be on Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone.

Exclusion Criteria:

  1. Patients having received intra-articular corticosteroid joint injection within the last 2-4 weeks.
  2. Patients with active systemic or joint infections.
  3. Women who are pregnant (pregnancy status will be self-reported)
  4. Patients under 18 years of age
  5. Non-English speakers
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02451748
Other Study ID Numbers  ICMJE 2015-0117
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Shiva Shahrara, University of Illinois at Chicago
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Illinois at Chicago
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE UCB Pharma
Investigators  ICMJE
Principal Investigator: Shiva Shahrara, PhD UIC
PRS Account University of Illinois at Chicago
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP