Clinical trial NCT02980887: Pulmonary Vascular Disease Phenomics Program PVDOMICS
Official title: Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics (PVDOMICS)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary arterial hypertension
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Columbia University
name: Weill Medical College of Cornell University
name: Johns Hopkins University
name: Mayo Clinic
name: University of Arizona
name: Vanderbilt University
First posted: 2016-12-02
Enrollment: 1195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with pulmonary hypertension, Pulmonary hypertension vascular, and healthy controls

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.

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

Primary outcomes:
measure: Precision based definitions of pulmonary vascular diseases (PVD)
timeFrame: Over 5 years
Secondary outcomes:
measure: Identification of biomarkers for PVD
timeFrame: 5 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Tufts University Medical Center
name: Nicholas S Hill, MD
role: STUDY_CHAIR
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Lei Xiao, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.