Endothelial Microparticles in Systemic Sclerosis Pulmonary Hypertension

NCT02331225 | Completed

• 1 other identifier: 8772
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Sclerosis; Pulmonary Hypertension; Scleroderma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Plasma PECAM+ endothelial microparticles

  Baseline

• Plasma E-selectin + endothelial microparticles

  Baseline

Study Arms (3)

Systemic sclerosis, no pulmonary hypertension

This group will be systemic sclerosis patients without pulmonary hypertension

Other: No intervention given

Systemic sclerosis/pulmonary hypertension

This group will be systemic sclerosis patients with pulmonary hypertension

Other: No intervention given

Healthy controls

These will be healthy age- and sex-matched controls

Other: No intervention given

Interventions

No intervention given OTHER

There is no intervention for this study

Healthy controls; Systemic sclerosis, no pulmonary hypertension; Systemic sclerosis/pulmonary hypertension

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Age \>18 years
• Meet American College of Rheumatology criteria for systemic sclerosis

You may not qualify if:

• 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:
• Age\>18 years
• Age- and sex-matched to SSc patients
• Coronary artery disease
• Uncontrolled hypertension (diastolic blood pressure\>120mmHg)
• Chronic obstructive pulmonary disease
• Chronic kidney disease
• Diabetes mellitus

Sponsors & Collaborators

• Louisiana State University Health Sciences Center in New Orleans: lead
• University of South Alabama: collaborator

Study Sites (1)

LSU Health Sciences Center

New Orleans, Louisiana, 70125, United States

Location

Related Publications (6)

• 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.

  PMID: 20339146 BACKGROUND

• 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.

  PMID: 18759303 BACKGROUND

• 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.

  PMID: 24016306 BACKGROUND

• 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.

  PMID: 18310479 BACKGROUND

• 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.

  PMID: 19782291 BACKGROUND

• 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.

  PMID: 30747487 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood will be retained.

MeSH Terms

Conditions

Scleroderma, Systemic; Hypertension, Pulmonary; Scleroderma, Diffuse

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: January 6, 2015
• Study Start: December 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: October 1, 2016
• Last Updated: December 16, 2016

Record last verified: 2016-12

Locations

US (1)