Study of Venous Endothelial Cells in Rheumatoid Arthritis
30 de marzo de 2021 actualizado por: Elizabeth Blair Solow, University of Texas Southwestern Medical Center
Analysis of Endothelial Cells in Rheumatoid Arthritis
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.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
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.
Tipo de estudio
De observación
Inscripción (Actual)
56
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
Texas
-
Dallas, Texas, Estados Unidos, 75390
- University of Texas Southwestern
-
Dallas, Texas, Estados Unidos, 75235
- Parkland Memorial Hospital
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
Rheumatoid arthritis patients will be selected from arthritis clinics associated with UT Southwestern Medical Center and Parkland Memorial Hospital.
Healthy controls will be collected from primary care clinics who refer to these specialty clinics.
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
|---|
|
Uncontrolled Rheumatoid Arthritis
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
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
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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Endothelial cell protein expression by immunofluorescence microscopy of endothelial nitric oxide synthase, nitrotyrosine, nuclear factor kappa B.
Periodo de tiempo: 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.
|
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.
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Serum cytokines analysis by cytometric bead array
Periodo de tiempo: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
|
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
Periodo de tiempo: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
|
Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Elizabeth B Solow, MD, University of Texas
- Investigador principal: David Karp, MD, PhD, University of Texas
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001 Dec;44(12):2737-45. doi: 10.1002/1529-0131(200112)44:123.0.CO;2-%23.
- Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F. Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. Atherosclerosis. 1997 Feb 28;129(1):111-8. doi: 10.1016/s0021-9150(96)06018-2.
- Vaudo G, Marchesi S, Gerli R, Allegrucci R, Giordano A, Siepi D, Pirro M, Shoenfeld Y, Schillaci G, Mannarino E. Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity. Ann Rheum Dis. 2004 Jan;63(1):31-5. doi: 10.1136/ard.2003.007740.
- Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005 Feb;52(2):402-11. doi: 10.1002/art.20853.
- Gonzalez-Juanatey C, Llorca J, Sanchez-Andrade A, Garcia-Porrua C, Martin J, Gonzalez-Gay MA. Short-term adalimumab therapy improves endo-thelial function in patients with rheumatoid arthritis refractory to infliximab. Clin Exp Rheumatol. 2006 May-Jun;24(3):309-12.
- Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ. C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis. Rheumatology (Oxford). 2008 Dec;47(12):1780-4. doi: 10.1093/rheumatology/ken386. Epub 2008 Oct 14.
- Schwartz R, Osborne-Lawrence S, Hahner L, Gibson LL, Gormley AK, Vongpatanasin W, Zhu W, Word RA, Seetharam D, Black S, Samols D, Mineo C, Shaul PW. C-reactive protein downregulates endothelial NO synthase and attenuates reendothelialization in vivo in mice. Circ Res. 2007 May 25;100(10):1452-9. doi: 10.1161/01.RES.0000267745.03488.47. Epub 2007 Apr 19.
- Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinski T, Luscher TF. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation. 1998 Jun 30;97(25):2494-8. doi: 10.1161/01.cir.97.25.2494.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de agosto de 2011
Finalización primaria (Actual)
1 de agosto de 2019
Finalización del estudio (Actual)
1 de diciembre de 2020
Fechas de registro del estudio
Enviado por primera vez
6 de marzo de 2014
Primero enviado que cumplió con los criterios de control de calidad
8 de junio de 2015
Publicado por primera vez (Estimar)
11 de junio de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
2 de abril de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
30 de marzo de 2021
Última verificación
1 de marzo de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- STU 012011-034
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .