Study of Venous Endothelial Cells in Rheumatoid Arthritis
30 de março de 2021 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
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 estudo
Observacional
Inscrição (Real)
56
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Texas
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Dallas, Texas, Estados Unidos, 75390
- University of Texas Southwestern
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Dallas, Texas, Estados Unidos, 75235
- Parkland Memorial Hospital
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 75 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Sim
Gêneros Elegíveis para o Estudo
Tudo
Método de amostragem
Amostra Não Probabilística
População do estudo
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.
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
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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. |
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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.
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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.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Endothelial cell protein expression by immunofluorescence microscopy of endothelial nitric oxide synthase, nitrotyrosine, nuclear factor kappa B.
Prazo: 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.
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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.
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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.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Serum cytokines analysis by cytometric bead array
Prazo: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
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Interleukin-1, Interleukin-6, Tumor Necrosis Factor -alpha
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Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
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Flow mediated dilation assessed in the brachial artery by ultrasound
Prazo: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
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Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Elizabeth B Solow, MD, University of Texas
- Investigador principal: David Karp, MD, PhD, University of Texas
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
1 de agosto de 2011
Conclusão Primária (Real)
1 de agosto de 2019
Conclusão do estudo (Real)
1 de dezembro de 2020
Datas de inscrição no estudo
Enviado pela primeira vez
6 de março de 2014
Enviado pela primeira vez que atendeu aos critérios de CQ
8 de junho de 2015
Primeira postagem (Estimativa)
11 de junho de 2015
Atualizações de registro de estudo
Última Atualização Postada (Real)
2 de abril de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
30 de março de 2021
Última verificação
1 de março de 2021
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- STU 012011-034
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