Endothelial Microparticles in Systemic Sclerosis Pulmonary Hypertension

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ClinicalTrials.gov Identifier: NCT02331225

Recruitment Status : Completed

First Posted : January 6, 2015

Last Update Posted : December 16, 2016

Sponsor:

Collaborator:

University of South Alabama

Information provided by (Responsible Party):

Matthew Lammi, Louisiana State University Health Sciences Center in New Orleans

Study Description

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.

Condition or disease	Intervention/treatment
Systemic Sclerosis Pulmonary Hypertension Scleroderma	Other: No intervention given

Study Design

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Study Type :	Observational
Actual Enrollment :	30 participants
Observational Model:	Cohort
Time Perspective:	Cross-Sectional
Official Title:	Endothelial Mircroparticles as a Biomarker of Pulmonary Hypertension in Systemic Sclerosis
Study Start Date :	December 2014
Actual Primary Completion Date :	July 2016
Actual Study Completion Date :	October 2016

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Hypertension Systemic scleroderma

MedlinePlus related topics: Pulmonary Hypertension Scleroderma

Genetic and Rare Diseases Information Center resources: Systemic Scleroderma

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Systemic sclerosis, no pulmonary hypertension This group will be systemic sclerosis patients without pulmonary hypertension	Other: No intervention given There is no intervention for this study
Systemic sclerosis/pulmonary hypertension This group will be systemic sclerosis patients with pulmonary hypertension	Other: No intervention given There is no intervention for this study
Healthy controls These will be healthy age- and sex-matched controls	Other: No intervention given There is no intervention for this study

Outcome Measures

Primary Outcome Measures :

Plasma VE-cadherin + endothelial microparticle levels [ Time Frame: Baseline ]
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

Secondary Outcome Measures :

Plasma PECAM+ endothelial microparticles [ Time Frame: Baseline ]
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
Plasma E-selectin + endothelial microparticles [ Time Frame: Baseline ]
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

Biospecimen Retention: Samples Without DNA

Blood will be retained.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
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.

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02331225

Locations

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United States, Louisiana
LSU Health Sciences Center
New Orleans, Louisiana, United States, 70125

Sponsors and Collaborators

Louisiana State University Health Sciences Center in New Orleans

University of South Alabama

More Information

Publications:

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.

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.

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. Epub 2013 Sep 9.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Matthew Lammi, Assistant Professor of Medicine, Louisiana State University Health Sciences Center in New Orleans
ClinicalTrials.gov Identifier:	NCT02331225
Other Study ID Numbers:	8772
First Posted:	January 6, 2015 Key Record Dates
Last Update Posted:	December 16, 2016
Last Verified:	December 2016

Additional relevant MeSH terms:

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Hypertension, Pulmonary Hypertension Scleroderma, Systemic Scleroderma, Diffuse Sclerosis Vascular Diseases	Cardiovascular Diseases Pathologic Processes Lung Diseases Respiratory Tract Diseases Connective Tissue Diseases Skin Diseases

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