Study of Venous Endothelial Cells in Rheumatoid Arthritis

NCT02468986 | Completed

• 1 other identifier: STU 012011-034
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Serum cytokines analysis by cytometric bead array

  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.

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• American Heart Association: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (8)

• 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.

  PMID: 14672888 BACKGROUND

• 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.

  PMID: 15693010 BACKGROUND

• 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.

  PMID: 11762933 BACKGROUND

• 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.

  PMID: 9069525 BACKGROUND

• 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.

  PMID: 16870100 BACKGROUND

• 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.

  PMID: 18854346 BACKGROUND

• 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.

  PMID: 17446434 BACKGROUND

• 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.

  PMID: 9657467 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum collected by serum separator tube. Will be processed and frozen at -80degrees.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Elizabeth B Solow, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

• David Karp, MD, PhD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSISTANT PROFESSOR

Study Record Dates

• First Submitted: March 6, 2014
• First Posted: June 11, 2015
• Study Start: August 1, 2011
• Primary Completion: August 1, 2019
• Study Completion: December 1, 2020
• Last Updated: April 2, 2021

Record last verified: 2021-03

Locations

US (2)