Endothelial Biomarkers of Systemic Sclerosis-associated Pulmonary Hypertension (BOSS-PH)

Novel Screening Strategy for Systemic Sclerosis-associated Pulmonary Hypertension Incorporating Endothelial Biomarkers

Systemic sclerosis (SSc, AKA scleroderma) is an autoimmune condition characterized by endothelial damage and progressive fibrosis of the skin and internal organs. One of the leading causes of morbidity and mortality in patients with SSc is pulmonary hypertension (PH), which is estimated to occur in up to 31% of high risk SSc patients. Early detection of patients with SSc-PH may lead to improved outcomes and although there have been concerted efforts to accurately screen for SSc-PH, these patients continue to present with advanced disease and suffer from poor survival. Therefore, better methods to screen for patients with PH and, perhaps more importantly, to screen for those at risk for PH development are desperately needed. Since PH and SSc are disorders originating from the endothelium, biomarkers that reflect endothelial damage are very promising tools to identify early disease. Such potential biomarkers include endothelial microparticles, asymmetric dimethylarginine (ADMA), pentraxin-3, and soluble endoglin. No previous study has used a combination of these biomarkers to detect the presence of PH in patients with SSc, or studied the novel concept of exercise-induced changes in biomarker levels. The investigators will collect the above listed endothelial biomarkers before and after exercise, and combine these levels with exercise echocardiogram findings, and routine clinical information to derive a composite detection score for the early identification of systemic sclerosis-associated PH.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension; Scleroderma
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Anticipated): 56

Contacts and Locations

• Study Contact: Name: Matthew R Lammi, MD, MSCR; Phone Number: 504-568-4634; Email: mlammi@lsuhsc.edu

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • University Medical Center-New Orleans
      • Contact: Matthew R Lammi, MD, MSCR; Phone Number: 504-568-4634; Email: mlammi@lsuhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of 26 patients with systemic sclerosis-associated pulmonary hypertension and 26 patients with systemic sclerosis but no diagnosis of current pulmonary hypertension.

Description

Inclusion Criteria:

• 1. Age >18 years 2. Meet American College of Rheumatology criteria for SSc

Exclusion Criteria:

1. Chronic kidney disease (estimated creatinine clearance <50mL/min)
2. Uncontrolled hypertension (diastolic blood pressure>120mmHg)
3. Acute coronary syndrome within the past 6 months
4. Chronic obstructive pulmonary disease
5. Diabetes mellitus
6. Hemolytic anemia
7. Active tobacco abuse

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Systemic sclerosis patients w/ PH; Pulmonary hypertension will be defined as a mean pulmonary artery pressure≥25mmHg on right heart catheterization	Other: No intervention; No intervention
Systemic sclerosis patients w/o PH; Pulmonary hypertension will be excluded based on all of the following echocardiogram features: estimated systolic pulmonary artery pressure<35mmHg and absence of right atrial or right ventricular (RV) enlargement and lack of qualitative RV dysfunction. If a subject has any of these echo features, they will be referred for right heart catheterization (RHC) and included in the appropriate group based on their RHC results.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite pulmonary hypertension detection score	A score will be derived by incorporating biomarkers, exercise echo results, pulmonary function tests, autoantibody status, 6-minute walk results, etc. into a linear regression model	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite pulmonary hypertension detection score	A score will be derived by incorporating biomarkers, exercise echo results, pulmonary function tests, autoantibody status, 6-minute walk results, etc. into a linear regression model	At 12 months

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Collaborators: Tulane University Health Sciences Center; Scleroderma Foundation; University Medical Center-New Orleans
• Investigators: Principal Investigator: Matthew R Lammi, MD, MSCR, LSU Health Sciences Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): October 31, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 1, 2018
• First Submitted That Met QC Criteria: March 7, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Biomarkers; Endothelial microparticles
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Connective Tissue Diseases; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Hypertension, Pulmonary
• Other Study ID Numbers: IRB 10033SM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No