Endothelial Microparticles in Systemic Sclerosis Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

Official title:

Endothelial Mircroparticles as a Biomarker of Pulmonary Hypertension in Systemic Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02331225
• Other study ID #: 8772
• Status: Completed
• Phase: N/A
• First received: December 18, 2014
• Last updated: December 15, 2016
• Start date: December 2014
• Est. completion date: October 2016

Study information

• Verified date: December 2016
• Source: Louisiana State University Health Sciences Center in New Orleans
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Systemic sclerosis (SSc, also known as scleroderma) is a disease characterized by fibrosis of the skin and organs, inflammation, and an abnormal endothelial cell lining inside of vessels. A common and deadly complication of SSc is pulmonary hypertension (PH), which is an abnormal elevation in the blood pressure within the lung blood vessels. Early identification and treatment of PH is important in SSc, and no clinical factors can predict which patients will develop PH with acceptable accuracy. A potential marker of PH in SSc is the presence of increased amounts of endothelial microparticles (EMPs), which are substances circulating in the blood that were released from damaged vessel wall endothelial lining. A main goal of this study is to investigate if there is a difference in EMP levels between SSc patients with and without PH. The investigators will also use human endothelial cells in a lab environment to test whether these EMPs isolated from SSc patients are actually causing damage to the vessel lining. Lastly, the investigators will investigate the potential benefit of a medication used after transplant, mycophenolate mofetil (MMF). This will be done by causing damage to isolated human endothelial cells and treating them with MMF. The main goal of this portion of our study is to see if EMP levels are reduced when cells are treated with MMF. Overall, the investigators anticipate the following outcomes of this study: 1) use EMP levels to differentiation patients with SSc who have PH from those without PH, 2) use EMPs to understand how endothelial damage occurs in SSc, and 3) use EMPs to help us develop new treatments for patients with vascular diseases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

For systemic sclerosis subjects:

Inclusion Criteria:

• Age >18 years

• Meet American College of Rheumatology criteria for systemic sclerosis

Exclusion Criteria:

• Chronic kidney disease (estimated creatinine clearance <50mL/min)

• Uncontrolled hypertension (diastolic blood pressure>120mmHg)

• Acute coronary syndrome within the past 6 months

• Chronic obstructive pulmonary disease

• Diabetes mellitus

• Hemolytic anemia

• Active tobacco abuse

For healthy control subjects:

Inclusion Criteria:

• Age>18 years

• Age- and sex-matched to SSc patients

Exclusion criteria:

• Coronary artery disease

• Uncontrolled hypertension (diastolic blood pressure>120mmHg)

• Chronic obstructive pulmonary disease

• Chronic kidney disease

• Diabetes mellitus

• Hemolytic anemia

• Active tobacco abuse

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Other:
• No intervention given
There is no intervention for this study

Locations

Country	Name	City	State
United States	LSU Health Sciences Center	New Orleans	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Louisiana State University Health Sciences Center in New Orleans	University of South Alabama

Country where clinical trial is conducted

United States, 

References & Publications (5)

Amabile N, Heiss C, Chang V, Angeli FS, Damon L, Rame EJ, McGlothlin D, Grossman W, De Marco T, Yeghiazarians Y. Increased CD62e(+) endothelial microparticle levels predict poor outcome in pulmonary hypertension patients. J Heart Lung Transplant. 2009 Oct;28(10):1081-6. doi: 10.1016/j.healun.2009.06.005. — View Citation

Amabile N, Heiss C, Real WM, Minasi P, McGlothlin D, Rame EJ, Grossman W, De Marco T, Yeghiazarians Y. Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1268-75. doi: 10.1164/rccm.200710-1458OC. — View Citation

Guiducci S, Distler JH, Jüngel A, Huscher D, Huber LC, Michel BA, Gay RE, Pisetsky DS, Gay S, Matucci-Cerinic M, Distler O. The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis. Arthritis Rheum. 2008 Sep;58(9):2845-53. doi: 10.1002/art.23735. — View Citation

Iversen LV, Østergaard O, Ullman S, Nielsen CT, Halberg P, Karlsmark T, Heegaard NH, Jacobsen S. Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis. Scand J Rheumatol. 2013;42(6):473-82. doi: 10.3109/03009742.2013.796403. — View Citation

Tual-Chalot S, Guibert C, Muller B, Savineau JP, Andriantsitohaina R, Martinez MC. Circulating microparticles from pulmonary hypertensive rats induce endothelial dysfunction. Am J Respir Crit Care Med. 2010 Jul 15;182(2):261-8. doi: 10.1164/rccm.200909-1347OC. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma VE-cadherin + endothelial microparticle levels	endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1	Baseline	No
Secondary	Plasma PECAM+ endothelial microparticles	endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1	Baseline	No
Secondary	Plasma E-selectin + endothelial microparticles	endothelial microparticles are expressed as microparticles per microliter of plasma. This is a cross-sectional analysis, so the measurements will be performed once, on study visit 1	Baseline	No