Clinical trial NCT02468986: Study of Venous Endothelial Cells in Rheumatoid Arthritis
Official title: Analysis of Endothelial Cells in Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: Bristol-Myers Squibb
First posted: 2015-06-11
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Endothelial cell protein expression by immunofluorescence microscopy of endothelial nitric oxide synthase, nitrotyrosine, nuclear factor kappa B.
timeFrame: 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:
measure: Serum cytokines analysis by cytometric bead array
timeFrame: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
measure: Flow mediated dilation assessed in the brachial artery by ultrasound
timeFrame: Measured once upon enrollment into study. Patient is followed-up 24 hours after by phone.
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
Study officials:
affiliation: University of Texas
name: Elizabeth B Solow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: David Karp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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