Study of Venous Endothelial Cells in Rheumatoid Arthritis

Study Overview
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Brief Summary
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Heart disease is the major contributor of early death in rheumatoid arthritis (RA) and is not influenced by traditional risk factors. Blood vessel dysfunction has been associated with heart disease and complications such as heart attack. The vessel dysfunction is thought to be mediated in part to inflammation. RA patients have evidence of vessel dysfunction seen on ultrasound that improves after medications are given. The purpose of this study is to evaluate patients with controlled or uncontrolled rheumatoid arthritis to determine if there is a difference in the protein expression in the cells that line the blood vessels compared to healthy people.

Detailed Description
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The study will consist of a cross sectional analysis of venous endothelial cells in rheumatoid arthritis patients who have controlled or uncontrolled disease and healthy controls. We will collect venous endothelial cells by placing an IV in antegrade position in the forearm and a thin wire will be inserted to collect the cells from the inner lining of the vein. The cells will processed and stained for markers of endothelial function and oxidative stress including endothelial nitric oxide synthase (eNOS), phospho-eNOS, nuclear factor kappa B (NFκB), and nitrotyrosine using immunofluorescence technique. Flow mediated dilation (FMD) by ultrasound of the brachial artery on the contralateral arm will be used as an additional marker of endothelial function. A blood sample will be taken for analysis of inflammatory markers (sedimentation rate, C-reactive protein) and cytokine analysis (IL-1, IL-6, TNFa) by cytokine bead array and flow cytometry.

Official Title
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Analysis of Endothelial Cells in Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rheumatoid arthritis: Age 18-75 years Rheumatoid arthritis defined by 1987 American College of Rheumatology criteria Attending clinic at University of Texas Southwestern Aston Clinic for Rheumatology or Parkland Arthritis Clinic. Healthy controls: - Age 18-75 years. Exclusion Criteria: Rheumatoid arthritis: Insulin dependent diabetes Cardiovascular or Cerebrovascular disease Tobacco use in last 24 months Uncontrolled blood pressure Uncontrolled cholesterol Pregnant or nursing Prednisone greater than 10mg per day Stable methotrexate dose for less than 4 weeks Undergoing Infliximab infusions Healthy controls: Insulin dependent diabetes Cardiovascular or Cerebrovascular disease Tobacco use in last 24 months Uncontrolled high blood pressure Uncontrolled cholesterol Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Uncontrolled Rheumatoid Arthritis<br>18-75 years old; Rheumatoid arthritis, defined by 1987 American College Rheumatology criteria; Attending clinic at Aston Center for Rheumatology or Parkland Rheumatology Clinic; Uncontrolled: Patients will be labeled as uncontrolled RA if Disease Activity Score (DAS) score is >3.2 and C-reactive protein (mg/dL) elevated above normal range. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. | |
| Controlled Rheumatoid Arthritis<br>18-75 years old; Rheumatoid arthritis, defined by 1987 American College Rheumatology criteria; Attending clinic at Aston Center for Rheumatology or Parkland Rheumatology Clinic; Controlled: Disease activity score (DAS) <3.2, normal C-reactive protein. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. | |
| Healthy Controls<br>18-75 years old. Excluding: Insulin dependent diabetes; Cardiovascular or Cerebrovascular disease (history of myocardial infarction, stroke, peripheral vascular disease); Tobacco use in the past 24 months; Uncontrolled hypertension (BP > 150/90) in the past 3 months; Uncontrolled hyperlipidemia (LDL>160) in the past 6 months; Pregnant or nursing. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial cell protein expression by immunofluorescence microscopy of endothelial nitric oxide synthase, nitrotyrosine, nuclear factor kappa B. | Immunofluorescence microscopy of frozen endothelial cells will be processed in batches to reduce bias. Cells are assessed for individual protein expression at study entry. Repeated collection of cells will not been done. | Cells are immediately processed following extraction and placed in -80 degree C freezer. Cells are then analyzed by immunofluorescence microscopy in batches of subjects. Patient is followed-up 24 hours after by phone. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokines analysis by cytometric bead array | Interleukin-1, Interleukin-6, Tumor Necrosis Factor -alpha | Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone. | 
| Flow mediated dilation assessed in the brachial artery by ultrasound |  | Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis