- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02451748
IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA
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
Study Overview
Status
Conditions
Intervention / Treatment
- 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
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
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- Outpatient Care Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Must meet 1987 Revised Criteria for the Classification of Rheumatoid Arthritis defined as the diagnosis of the referring physician.
- Persistent knee swelling (>ARA grade 2) for 2 weeks, and no recent intra-articular corticosteroid injection.
- Age 18 years and older.
- Must be on Disease modifying anti rheumatic drugs (DMARDs) such as methotrexate, plaquenil and/or prednisone.
Exclusion Criteria:
- Patients having received intra-articular corticosteroid joint injection within the last 2-4 weeks.
- Patients with active systemic or joint infections.
- Women who are pregnant (pregnancy status will be self-reported)
- Patients under 18 years of age
- Non-English speakers
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: 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.
|
Lab work to measure IL-7 and IL-7R
|
Other: 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.
|
Lab work to measure IL-7 and IL-7R
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 Names:
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 Names:
some patients are on 400mg/day of hydroxychloroquine.
some patients are on 300 mg/day and some patients are on 1000 mg/day dose of sulfasalazine
some patients are on 8mg/day of medrol
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
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
some patients are on 1000 mg/day of naproxen
some patients are on 20mg/day of leflunomide
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
some patients are on Humira 40mg q2weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
RA subjects treated with (DMARDs) only, blood will only be taken once at the subjects routine visit. An expected average of 4-6 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Shiva Shahrara, PhD, UIC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Peripheral Nervous System Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dermatologic Agents
- Reproductive Control Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Gout Suppressants
- Prednisone
- Triamcinolone
- Methotrexate
- Leflunomide
- Certolizumab Pegol
- Hydroxychloroquine
- Naproxen
- Sulfasalazine
Other Study ID Numbers
- 2015-0117 (Other Identifier: M D Anderson Cancer Center)
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.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
Assistance Publique - Hôpitaux de ParisSociete Francaise de RhumatologieRecruiting
-
Amsterdam UMC, location VUmcEuropean CommissionCompletedRheumatoId ArthritisNetherlands, Germany, Portugal, Italy, Hungary, Romania, Slovakia
-
University Hospital, ToulouseCompletedRheumatoId ArthritisFrance
-
David Grant U.S. Air Force Medical CenterCompleted
-
TcLand Expression S.A.European CommissionTerminatedRheumatoId ArthritisFrance, Netherlands, Turkey, Czechia, Israel
Clinical Trials on Lab Work
-
University of PittsburghNational Heart, Lung, and Blood Institute (NHLBI)CompletedHIV | Aging | Pulmonary Disease | COPDUnited States
-
Epidemiology Coordinating and Research Centre,...UnknownRheumatoid Arthritis | Inflammatory Arthritis | Psoriatic Arthritis | Cardiovascular Risk Factor | Ankylosing SpondylitisCanada
-
Ohio State University Comprehensive Cancer CenterRecruitingE-cigarette UseUnited States
-
Centre Hospitalier Universitaire de NiceUnknown
-
Medipol UniversityNot yet recruiting
-
Yale UniversityCompletedCognitive Impairment | Substance Abuse | Substance DependenceUnited States
-
Istanbul Training and Research HospitalCompleted
-
Brigham and Women's HospitalCambridge Medical Technologies, LLCActive, not recruitingSepsis | Infectious Disease | Lactate Blood Increase | Sepsis BacterialUnited States
-
Nantes University HospitalUnknown
-
Healthy.io Ltd.CompletedHypertension | DiabetesUnited States