Pulmonary Vascular Disease Phenomics Program PVDOMICS (PVDOMICS)

Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS)

It is recognized that patients with various forms of heart and lung disease exhibit varying degrees of pulmonary hypertension, pulmonary vascular remodeling, and right ventricular dysfunction. The genetic, molecular, and cellular processes driving these phenomena are not well understood. Rapid advances in high throughput omic methodology, combined with powerful bioinformatics and network biology capability, have created the opportunity to conduct studies that broadly search for homologies and differences across the spectrum of disease states associated with pulmonary hypertension, and determinants of the spectrum of right ventricular compensation that accompanies these conditions

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Other: No Intervention

Detailed Description

The protocol is designed to lead to new understanding of patients with pulmonary hypertension and right heart dysfunction, based on molecular, clinical, hemodynamic and radiographic characteristics. New classifications will be a product of association of these in depth phenotypic descriptions with specific molecular mechanisms of pathogenesis. The protocol will be implemented to lead to identification of both sub-phenotypes of lung vascular disease and to biomarkers of disease that may be useful for early diagnosis or for assessment of interventions to prevent or treat this condition.

A longitudinal study in a subset of the participants enrolled in the parent cross-sectional study will:

1. Retest participants at a minimum 6 month interval from initial evaluation to collect a core set of clinical and OMICS features. This will include survival, clinical staging, clinical group assignment, 6-minute walk, echocardiography, and blood for a broad collection of selected OMICS tests, to include proteomics and other variables found to be informative in the initial set.
2. Associate and compare OMICS data with clinical sets and OMICS clusters between baseline and follow-up interval, with attention to reproducibility, predictive capacity as biomarkers for diagnosis, disease progression, phenotypic changes, functional capacity, therapeutic response and survival.

• Study Type: Observational
• Enrollment (Actual): 1195

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • University of Arizona Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10032
      • Columbia University School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with pulmonary hypertension, Pulmonary hypertension vascular, and healthy controls

Description

Cross-sectional (parent) study:

Inclusion Criteria:

Patients ages >18 years of age referred for right heart catheterization for further evaluation of known PVD or to be at risk for PVD due to established cardiac disease or pulmonary disease

• Able to perform complete diagnostic testing listed subsequently (cardiac catheterization, echo, exercise test, PFT's, ECG, chest CT, quality of life questionnaires, ventilation/perfusion scan, cardiac MRI, body composition bioimpedance, and sleep study)
• Subject signs informed consent to perform required testing for the protocol

Exclusion Criteria:

Dialysis dependent renal function; In the clinician's opinion, too ill to perform the protocol testing; Pregnant or nursing

Longitudinal study:

Inclusion Criteria:

• Any PH, comparators or control participant previously enrolled in the parent PVDOMICS protocol with a minimum of six months post-enrollment
• Dialysis dependent renal function since the parent study acceptable

Exclusion Criteria:

Participant Level 1 (clinic visit):

• Transplant other than heart or lung
• In the clinician's opinion, too ill to perform L-PVDOMICS testing even if limited testing.
• Participants who withdrew from the parent PVDOMICS study
• Pregnant or nursing
• Concurrent participation in any investigational drug study or other clinical trial

Participant Level 2 (telephone visit):

• Transplant other than heart or lung
• Participants who withdrew from the parent PVDOMICS study

Participant Level 3 (medical chart review):

- Participants who withdrew from the parent PVDOMICS study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; Healthy controls No intervention as this is an observational study	Other: No Intervention; There is no intervention in this observational study
Pulmonary Vascular Disease; Pulmonary Vascular Disease at risk for pulmonary hypertension	Other: No Intervention; There is no intervention in this observational study
Pulmonary Hypertension; Those meeting WSPH/WHO group classifications 1-5 of pulmonary hypertension	Other: No Intervention; There is no intervention in this observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Precision based definitions of pulmonary vascular diseases (PVD)	OMICs analyses will be used to assign new class of PVD	Over 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of biomarkers for PVD	OMICs and other measures of disease	5 years

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Johns Hopkins University; Mayo Clinic; Columbia University; Brigham and Women's Hospital; Weill Medical College of Cornell University; Vanderbilt University; University of Arizona
• Investigators: Study Chair: Nicholas S Hill, MD, Tufts University Medical Center; Study Director: Lei Xiao, MD, National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Hemnes AR, Leopold JA, Radeva MK, Beck GJ, Abidov A, Aldred MA, Barnard J, Rosenzweig EB, Borlaug BA, Chung WK, Comhair SAA, Desai AA, Dubrock HM, Erzurum SC, Finet JE, Frantz RP, Garcia JGN, Geraci MW, Gray MP, Grunig G, Hassoun PM, Highland KB, Hill NS, Hu B, Kwon DH, Jacob MS, Jellis CL, Larive AB, Lempel JK, Maron BA, Mathai SC, McCarthy K, Mehra R, Nawabit R, Newman JH, Olman MA, Park MM, Ramos JA, Renapurkar RD, Rischard FP, Sherer SG, Tang WHW, Thomas JD, Vanderpool RR, Waxman AB, Wilcox JD, Yuan JX, Horn EM; PVDOMICS Study Group. Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease. J Am Coll Cardiol. 2022 Aug 16;80(7):697-718. doi: 10.1016/j.jacc.2022.05.038.
• Tang WHW, Wilcox JD, Jacob MS, Rosenzweig EB, Borlaug BA, Frantz RP, Hassoun PM, Hemnes AR, Hill NS, Horn EM, Singh HS, Systrom DM, Tedford RJ, Vanderpool RR, Waxman AB, Xiao L, Leopold JA, Rischard FP. Comprehensive Diagnostic Evaluation of Cardiovascular Physiology in Patients With Pulmonary Vascular Disease: Insights From the PVDOMICS Program. Circ Heart Fail. 2020 Mar;13(3):e006363. doi: 10.1161/CIRCHEARTFAILURE.119.006363. Epub 2020 Feb 24.

Helpful Links

• PVDOMICS study protocol

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: November 30, 2016
• First Posted (Estimated): December 2, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Pulmonary arterial hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Vascular Diseases; Pulmonary Arterial Hypertension
• Other Study ID Numbers: 16-860

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan for sharing with outside network investigators is being developed.
• IPD Sharing Time Frame: Being decided
• IPD Sharing Access Criteria: Being decided
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF