Pulmonary Vascular Disease Phenomics Program PVDOMICS (PVDOMICS)

• ClinicalTrials.gov Identifier: NCT02980887
• Recruitment Status: Active, not recruiting
• First Posted: December 2, 2016
• Last Update Posted: January 18, 2024
• Sponsor: The Cleveland Clinic
• Collaborators: Brigham and Women's Hospital; Columbia University; Weill Medical College of Cornell University; Johns Hopkins University; Mayo Clinic; University of Arizona; Vanderbilt University
• Information provided by (Responsible Party): The Cleveland Clinic

Tracking Information

• First Submitted Date: November 30, 2016
• First Posted Date: December 2, 2016
• Last Update Posted Date: January 18, 2024
• Study Start Date: November 2016
• Estimated Primary Completion Date: December 31, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2016)

Precision based definitions of pulmonary vascular diseases (PVD) [ Time Frame: Over 5 years ]

OMICs analyses will be used to assign new class of PVD

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 30, 2016)

Identification of biomarkers for PVD [ Time Frame: 5 years ]

OMICs and other measures of disease

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pulmonary Vascular Disease Phenomics Program PVDOMICS
• Official Title: Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS)
• Brief Summary: 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

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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Samples for Omics analyses, including DNA

• Sampling Method: Non-Probability Sample
• Study Population: Patients with pulmonary hypertension, Pulmonary hypertension vascular, and healthy controls
• Condition: Pulmonary Arterial Hypertension

Intervention

Other: No Intervention

There is no intervention in this observational study

Study Groups/Cohorts

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

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 14, 2022): 1195
• Original Estimated Enrollment (submitted: November 30, 2016): 1500
• Estimated Study Completion Date: December 31, 2029
• Estimated Primary Completion Date: December 31, 2029 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02980887
• Other Study ID Numbers: 16-860
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Plan for sharing with outside network investigators is being developed.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Being decided
• Access Criteria: Being decided

• Current Responsible Party: The Cleveland Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: The Cleveland Clinic
• Original Study Sponsor: Same as current

Collaborators

• Brigham and Women's Hospital
• Columbia University
• Weill Medical College of Cornell University
• Johns Hopkins University
• Mayo Clinic
• University of Arizona
• Vanderbilt University

Investigators

• Study Chair: Nicholas S Hill, MD; Tufts University Medical Center
• Study Director: Lei Xiao, MD; National Heart, Lung, and Blood Institute (NHLBI)

• PRS Account: The Cleveland Clinic
• Verification Date: January 2024