Clinical trial NCT02331225: Endothelial Microparticles in Systemic Sclerosis Pulmonary Hypertension
Official title: Endothelial Mircroparticles as a Biomarker of Pulmonary Hypertension in Systemic Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Sclerosis
Pulmonary Hypertension
Scleroderma
Lead sponsor: Louisiana State University Health Sciences Center in New Orleans
Sponsor class: OTHER
Collaborators: name: University of South Alabama
First posted: 2015-01-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: There will be 3 groups: systemic sclerosis subjects with pulmonary hypertension, systemic sclerosis subjects without pulmonary hypertension, and healthy age- and sex-matched controls.

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Plasma VE-cadherin + endothelial microparticle levels
timeFrame: Baseline
Secondary outcomes:
measure: Plasma PECAM+ endothelial microparticles
timeFrame: Baseline
measure: Plasma E-selectin + endothelial microparticles
timeFrame: Baseline
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: LSU Health Sciences Center
state: Louisiana
Study officials:
References:
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. Epub 2010 Mar 25.
citation: Guiducci S, Distler JH, Jungel 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.
citation: Iversen LV, Ostergaard 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. Epub 2013 Sep 9.
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. Epub 2008 Feb 28.
citation: 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.
citation: Lammi MR, Saketkoo LA, Okpechi SC, Ghonim MA, Wyczechowska D, Bauer N, Pyakurel K, Saito S, deBoisblanc BP, Boulares AH. Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers. Respirology. 2019 Jul;24(7):675-683. doi: 10.1111/resp.13500. Epub 2019 Feb 12.