Recruiting

Multimodal and Multidisciplinary Approach to optimize Diagnostic, Prognostic, and Therapeutic management of Patients with Nonischemic Cardiomyopathies and Arrhyhmogenic-Inflammatory phenotypes

Status: Recruiting

Location: IRCCS San Raffaele Scientific Institute

Conditions: IRCCS San Raffaele Scientific Institute

City/State:

Milan, Italy

Contact Information:

Giovanni Peretto, MD
+39 (022) 643-7482
[email protected]

Brief Summary:

  • nonischemic cardiomyopathies (NICM) constitute a heterogeneous group of diseases characterized by distinct structural and functional myocardial abnormalities in the absence of obstructive epicardial coronary artery disease. To date, there is a huge lack of knowledge related to two main aspects of NICM, namely the “arrhythmogenic” and the “inflammatory” phenotypes, hereby named as AINICM. This study is multicenter, observational and both retrospective and prospective and aims to answer multiple unsolved questions in the field of AINICM:
  • Improving the diagnostic workup
  • Identifying disease-specific signatures
  • Working our models for risk prediction
  • Tailoring treatment strategies
  • Allowing direct comparison among specific NICM subgroups, i.e. dilated, hypertrophic, nondilated, arrhythmogenic, restrictive, and other rare cardiomyopathies.
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Role of Endomyocardial Biopsy and Etiology-based Treatment in Patients With Inflammatory Heart Disease in Arrhythmic and Non-arrhythmic Clinical Presentations: an Integrated Approach for the Optimal Diagnostic and Therapeutic Management

Status: Recruiting

Location: IRCCS San Raffaele Scientific Institute

Conditions: IRCCS San Raffaele Scientific Institute

City/State:

Milan, Italy

Contact Information:

Giovanni Peretto, MD
+39 (022) 643-7482
[email protected]

Brief Summary:

this multicenter registry, both retrospective and prospective, aims at answering multiple questions about myocarditis, with special attention to arrhythmic manifestations. Patients with myocarditis proven at least by endomyocardial biopsy and/or cardiac magnetic resonance will be enrolled, and characterized by means of multimodality diagnostic workup, both at baseline and during follow-up. The following unsolved questions will be addressed:

-to report the prevalence of arrhythmias in myocarditis

-to describe the relationships between arrhythmia features and myocardial inflammatory status

-to identify predictors of sudden cardiac death in acute myocarditis and chronic inflammatory cardiomyopathy with arrhythmic vs. non-arrhythmic clinical onset

-to investigate safety and effectiveness of immunomodulatory treatment strategies in arrhythmic and non-arrhythmic myocarditis

-to investigate safety and effectiveness of catheter ablation ablation to target myocarditis-associated arrhythmias

-to describe clinical presentation and arrhythmic outcomes of genetic forms of myocarditis

-to describe clinical presentation and arrhythmic outcomes of myocarditis associated with systemic rheumatologic diseases

 

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Full-Field Optical Coherence Tomography (FFOCT) for Evaluation of Bronchoscopic Small Biopsy Specimens

Status: Recruiting

Location: Johns Hopkins University

Conditions: Johns Hopkins University

City/State:

Baltimore, Maryland

Contact Information:

Jeffrey Thiboutot, MD
410-502-2533
[email protected]

Brief Summary:

This study sets out to register imaging of small biopsy specimens obtained during bronchoscopy using full-field optical coherence tomography against standard histologic evaluation.
Detailed Description:

Small biopsy specimens obtained through bronchoscopy are commonly employed for the diagnosis and staging of thoracic malignancies. Diagnostic yield is dependent on tissue quality and quantity in specimens obtained through bronchoscopy, and it is thus important to ensure adequate sampling. Rapid on-site cytology (ROSE) is a method used by having a cytotechnologist at the bedside to prepare and analyze specimens to improve the quality of tissue acquisition during bronchoscopy. Although effective, ROSE expertise is not always available to proceduralists, is costly, and reproducible techniques that can be deployed across multiple tiers of institutions are needed across the globe.

Optical coherence tomography (OCT) is an emerging technique which may provide real-time imaging with resolution approaching that of typical histopathology. This has several benefits over ROSE using histopathologic evaluation including rapid imaging with minimal tissue processing, preservation of tissue specimens for molecular testing, enhanced intracellular contrast, and adaptation to machine learning approaches to allow for a reproducible and consistent result. In fact, full-field OCT has recently been applied in several tissue types for evaluation of adequacy of pathologic specimens and evaluation of malignancy, among others. To the best of the investigators’ knowledge, this technology has not yet been evaluated for assessment of specimen quality in bronchoscopic procedures.

Thus, the investigators propose a study of full-field OCT for evaluation of small biopsy specimens obtained through bronchoscopy. The investigators aim to demonstrate the feasibility of this technology in the workflow of bronchoscopy and compare to current evaluation methods including rapid on-site evaluation (ROSE). ROSE is commonly used to evaluate adequacy of tissue diagnosis during bronchoscopic procedures including at this institution. However, studies have not shown definitive benefits over bronchoscopy without ROSE, and current expert guidelines suggest bronchoscopy with Endobronchial Ultrasound (EBUS) transbronchial needle aspiration (TBNA) may be performed with or without ROSE.

Full-field OCT has several potential benefits compared to ROSE, including rapid analysis with minimal tissue processing and preservation of tissue for further molecular testing. In addition, OCT has been used to assess surgical biopsy specimens in a non-destructive manner, so the tissues can be analyzed after imaging using standard cytological and pathological methods. Full-field OCT evaluation may be applied to other diseases in addition to further augmenting the diagnostic ability through the use of machine learning approaches.

 

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Role of Novel ILR in the Management of PVCs

Status: Recruiting

Location: Centerpoint Medical Center, Kansas City Heart Rhythm Institute, Overland Park Regional Medical Center

Conditions: Centerpoint Medical Center, Kansas City Heart Rhythm Institute, Overland Park Regional Medical Center

City/State:

Overland Park, Kansas

Independence, Missouri

Kansas City, Missouri

Contact Information:

Donita Atkins
816-651-1969
[email protected]

Brief Summary:
This prospective, observational study is a single center clinical registry of patients referred for management of symptomatic or asymptomatic Premature Ventricular Contractions (PVCs). Subjects will be followed through 12 months. The study will enroll approximately 50 patients.
Detailed Description:
This study is intended to monitor patients presenting with Premature Ventricular Contractions (PVCs) and ventricular arrhythmias using implantable loop recorders (ILRs) from the time of their initial presentation of PVCs to assess for the incidence of all cardiac arrhythmias detected with long term monitoring in this population. It is also intended to evaluate for clinical, biomarker and radiological evidence of myocarditis in this cohort to understand association with incident arrhythmias and understand the role of implantable loop recorders (ILRs)in managing these patients.
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Pulmonary Care and Research Collaborative Patient Registry

Status: Recruiting

Location:

Conditions:

City/State:

Boston, Massachusetts

Contact Information:

Aliaa Barakat, PhD
617-895-6636
[email protected]

Arthur Dea, BA
617-895-9879
[email protected]

Brief Summary:
The purpose of this research study is to build and maintain a registry of people with interstitial lung disease (ILD). Medical information collected for this registry may be used to advance ILD and pulmonary research and improve patient care. This is an observational registry. Participants will not receive any investigational treatments or investigational drugs as part of their participation in this registry.
Detailed Description:
The registry will contain longitudinal medical histories of ILD patients. The creation and curation of the registry with utilize release of information services, biomedical informatics methods and human expert reviews. Among the registry’s long-term goals is to utilize its data and informatics resources to study and advance ILD diagnosis and treatment. The registry will be developed with a set of capabilities to consistently, repeatedly, and economically build research-grade datasets that allow cohort development from natively unstructured and non-standard phenotypic clinical and imaging data.
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Rheumatology Patient Registry and Biorepository

Status: Recruiting

Location: Yale-New Haven Hospital

Conditions: Yale-New Haven Hospital

City/State:

New Haven, Connecticut

Contact Information:

Nicolas Page
203-737-5571
[email protected]

Brief Summary:
To facilitate clinical, basic science, and translational research projects involving the study of rheumatic diseases.
Detailed Description:
A rheumatology biorepository will be created to permit comparative analyses between the rheumatic diseases in order to increase the understanding of disease pathogenesis. Patients seen at Yale clinics diagnosed with rheumatic diseases are invited to participate in this study. These rheumatic diseases include, but are not limited to: adult onset Still’s disease, ankylosing spondylitis, psoriatic arthritis, reactive arthritis, antiphospholipid syndrome, systemic lupus erythematosus, Behcet’s disease, dermatomyositis, polymyositis, giant cell arteritis and other vasculitides, Lyme’s disease, mixed connective tissue disease, polymyalgia rheumatica, rheumatoid arthritis, sarcoidosis, systemic sclerosis (scleroderma), Sjogren’s syndrome, and undifferentiated connective tissue disease.
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Mayo AVC Registry and Biobank

Status: Recruiting

Location: Mayo Clinic in Rochester, University of Kansas Medical Center

Conditions: Mayo Clinic in Rochester, University of Kansas Medical Center

City/State:

Rochester, Minnesota

Contact Information:

Nicholas Wozniak
+1 507 2558794
[email protected]

Anwar A Chahal, Ph.D.
[email protected]

Brief Summary:

Arrhythmogenic ventricular cardiomyopathy (AVC) is a genetic condition which affects the heart and can lead to heart failure and rhythm problems, of which, sudden cardiac arrest or death is the most tragic and dangerous. Diagnosis and screening of blood-relatives is very difficult as the disease process can be subtle, but sufficient enough, so that the first event is sudden death.

The Mayo Clinic AVC Registry is a collaboration between Mayo Clinic, Rochester, USA and Papworth Hospital, Cambridge University Hospitals, Cambridge, UK. The investigators aim to enroll patients with a history of AVC or sudden cardiac death which may be due to AVC, from the US and UK. Family members who are blood-relatives will also be invited, including those who do not have the condition. Data collected include symptoms, ECG, echocardiographic, MRI, Holter, loop recorder, biopsies, exercise stress testing, blood, buccal and saliva samples.

Objectives of the study:

  1. Discover new genes or altered genes (variants) which cause AVC
  2. Identify biomarkers which predict (2a) disease onset, (2b) disease progression, (2c) and the likelihood of arrhythmia (ventricular, supra-ventricular and atrial fibrillation)
  3. Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally using clinical, electrocardiographic and imaging data.
  4. Characterize desmosomal changes in buccal mucosal cells with genotype and validate with gold-standard endomyocardial biopsies
Detailed Description:

Sudden cardiac arrest (SCA) accounts for over 360,000 deaths in the US and 400,000 in Europe per annum, including thousands under the age of 40 who die unexpectedly and without warning. Whilst the majority of SCAs are triggered by heart attacks, in those under the age of 40 years this tends to be due to genetic heart disease, which if identified early may save lives of other family members. Epidemiological and post-mortem studies have shown arrhythmogenic ventricular cardiomyopathy (AVC) as a leading cause of SCA, responsible for up to 25% of deaths in this age group.

AVC is a highly clinically and genetically heterogeneous condition, which results in fibro-fatty replacement of myocardium which may lead to ventricular dysfunction, heart failure, electrical rhythm disturbances and SCD. Although AVC predominantly affects the right ventricle (ARVC), it can affect both the right and left ventricle, or the LV in isolation (ALVC) and result in a type of dilated cardiomyopathy (DCM) with a propensity for arrhythmia (aDCM). Recent reports of aDCM with a familial distribution suggests this is undiagnosed AVC, reflecting heterogeneity and limited understanding. AVC is considered a disease of the desmosome (cell-adhesion proteins) and this has led to identification of desmosomal mutations (plakoglobin, plakophilin-2, desmoplakin, desmoglein-2 and desmocollin), mostly inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity. Non-desmosomal genes have also been discovered (desmin, titin, RYR2, transforming growth factor -3, transmembrane protein 43 and phospholamban). Together, these only account for 50-60% of known AVc-related mutations, with the remainder being genetically undetermined. Additionally, multiple mutations also exist within families and within individuals further compounding the complexity of AVC. Inter and intra-familial variability is inexplicable with current knowledge, and suggests epigenetic and environmental factors contributing to phenotype. Disease expression is highly variable even amongst members of the same family with the same mutation making clinical detection and cascade screening a challenge. Finally, predicting which patients are at risk of SCD who have AVC or may have AVC is difficult and potentially lethal. Since SCD can be the first lethal and tragic manifestation of the disease, optimizing screening strategies is of paramount importance. The long-term goals of this program are to leverage our well-phenotyped cohort of patients with AVC at Mayo Clinic and Papworth Hospital, University of Cambridge, , enroll others and to discover novel pathogenic variants, correlate genotype with phenotype, and develop robust screening tools for the diagnosis of AVC and preventing SCD.

Overall hypothesis: that the onset of AVC can be reliably and accurately predicted in first-degree relatives of index cases using genetic, electrocardiographic (ECG) and imaging data.

Aim #1: Identify novel candidate genes and variants associated with AVC (including cases involving the right, left and the dilated cardiomyopathy types). This aim will be accomplished using next generation sequencing of probands-family member trios “genomic familial triangulation” approach and an innovative bioinformatics, statistical, and systems based biology approach.

Aim #2: Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally using clinical, ECG and imaging data to 2a. predict disease onset; 2b. predict disease progression; and 2c. predict the likelihood of arrhythmia (ventricular, supra-ventricular and atrial fibrillation).

Aim #3: Combine registries from the Mayo Clinic, Rochester, USA and Papworth Hospital, University of Cambridge, UK, to study longitudinal data and correlate genotype with phenotype.

Aim #4: Characterize desmosomal changes in buccal mucosal cells with genotype and validate with gold-standard endomyocardial biopsies.

Project approval:

This study is approved by the Mayo Clinic IRB and Papworth Hospital NHS Foundation Trust for collation of existing data to develop the registry.

New directions for the project will seek appropriate approval by the IRB of each site in due course.

Recruitment strategy:

Patients who are already seen at Mayo Clinic Rochester and Papworth Hospital sites will be enrolled, provided research authorization is active. A HIPPA waiver has been approved as the registry collates existing data. Standard Mayo Clinic policy is to inform patients that clinical data can be utilized for research purposes, and patients are asked to specifically decline research authorization if they wish to opt out. A similar system is in place at Papworth Hospital.

For specific aims which require blood or other bio-specimens for the biobank, a separate IRB will be utilized and this requires a signed consent form.

Baseline data includes but is not limited to the following, at index presentation or screening visit for first-degree relatives:

  • Baseline demographics
  • Clinical history
  • Examination findings including features suggestive of cardio-cutaneous syndromes etc.
  • Family history of at least 3 generations. An online tool will be utilized for generating a pedigree (http://www.progenygenetics.com/online-pedigree)
  • Serial ECG data (12-lead, signal-averaged and Brugada protocols)
  • Continuous ECG monitoring data (Holter, extended-Holter, event recorders, implantable loop recorders etc.)
  • Imaging data (echocardiography, cardiac MRI, cardiac CT)
  • Cardiopulmonary exercise testing or exercise stress testing
  • Questionnaires on exercise capacity, activities of daily living (these will be approved by the IRB if self-completed by patients)
  • Cardiac catheterization data
  • Existing genotyping data (including methods used)
  • Where available, endomyocardial biopsy data

For clinical follow-up visits and screening follow-up of first-degree relatives, in addition to those test above, the following will be collected:

  • Cardiac implantable electronic devices data
  • Cardiac electrophysiology studies, and where catheter ablation delivered, this will be recorded

Biobank for genotyping and novel variant discovery:

Current guidelines recommend genetic testing for index cases and blood-relatives. Where this is performed and available, this will be collected.

Probands and their blood-relatives will be invited to participate in this optional component of the study. Blood, saliva and buccal scrapings will be collected from probands and blood relatives, to identify current pathogenic variants associated with AVC, and to discover novel variants.

Biobank for novel biomarker discovery:

Blood will be stored at baseline and subsequent visits to test for known blood-biomarkers of disease progression (such as high-sensitivity cardiac troponins, natriuretic peptides, high-sensitivity CRP and cytokines). Blood will also be stored for high throughput ‘omics (transcriptomics, metabolomics and proteomics) to identify novel biomarkers which reflect disease progression, prognostication and crucially help illuminate new biological pathways.

Annual Clinical Assessment:

Most patients with AVC are followed-up annually or more frequently dependent upon symptoms. At each follow-up an ECG and/or Holter is usually performed. The investigators will ensure each site performs this consistently. Data generated will be used for the registry. In addition, investigators may contact patients by telephone to assess symptoms (following IRB approval).

Follow-up at every 3-year interval:

Clinical guidelines for screening first-degree relatives recommend follow-up approximately every 3 years, as phenotype expression can be delayed (with the exception of familial cases where a pathogenic variant has been identified, and the blood-relative is negative). Thus, this time period has been chosen for subsequent follow-up visits, where patients will be re-assessed by 2010 Task Force Criteria for evidence of AVC. This follow-up visit will include:

  • Clinical history
  • Examination
  • ECG (12-lead and signal-averaged)
  • Holter monitoring
  • Repeat cardiac MRI
  • Exercise testing (CPET or treadmill)

It is our objective to continue this registry indefinitely, in order to capture adequate event rates for valid and accurate modelling to predict disease progression.

Data Collation and Management:

The investigators will use the REDCap (Research Electronic Data Capture) tool for completion of case report forms at enrollment and follow-up visits (link to a demonstration website https://projectredcap.org). The servers are based in-house at Mayo Clinic, with access only provided to approved study personnel. No personal identifiable information will be collated online. All cases will have a unique study ID, with the key to link each subject ID to patient identifiable data located at each site, and only available to the PIs and senior research personnel.

The data stored is considered confidential and will not be disclosed to any 3rd parties, with the exception of the participants clinical health-care providers responsible for the patient’s welfare.

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Interstitial Lung Disease Research Unit Biobank

Status: Recruiting

Location: University of Kansas Medical Center

Conditions: University of Kansas Medical Center

City/State:

Kansas City, Kansas

Contact Information:

Kimberly Lovell, Ph.D.
913-588-6067
[email protected]

Brief Summary:
Establish a interstitial lung disease (ILD) registry and biorepository to lead towards a further understanding of the disease.
Detailed Description:
The University of Kansas ILD and Rare Lung Disease clinic sees hundreds of new patients per year. The investigators would like to leverage this resource to develop an Interstitial Lung Disease Research Unit (ILDRU) repository and database to help develop new methods for early diagnosis, uncover underlying genetic and environmental risk factors, as well as potential treatment targets in the broad range of interstitial lung diseases and rare lung diseases (RLD).
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A Study of the Natural Progression of Interstitial Lung Disease

Status: Recruiting

Location: University of Chicago

Conditions: University of Chicago

City/State:

Chicago, Illinois

Contact Information:

Spring Maleckar
773-834-4053

Brief Summary:
We propose to acquire data and blood samples on all patients being cared for by the Interstitial Lung Disease (ILD) program. Additionally, we will collect data and blood samples from a control group for comparator purposes. In doing so, we will be able to describe the “phenotypic” expression of these diseases.
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Role of Genetic Factors in the Development of Lung Disease

Status: Recruiting

Location:

Conditions:

City/State:

Bethesda, Maryland

Contact Information:

Tatyana Worthy, R.N.
(301) 827-1376
[email protected]

Joel Moss, M.D.
(301) 496-1597
[email protected]

Brief Summary:

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease.

The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers.

Optional CT Sub-study

The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease status.

This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.

Detailed Description:

This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.
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