Clinical Trials Logo

Clinical Trial Summary

Autophagy is considered an important component of Heart failure progression. Deubiquitination enzymes play an important role in autophagy. An important regulatory process within the autophagy pathway is ubiquitination. Ubiquitination targets proteins for degradation. On the contrary, de-ubiquitinating proteins (such as UCHL1) reverses this process. Studies have demonstrated deubiquitination to be linked to certain pathological processes, such as heart failure. UCHL1 will be examined as a potential marker of disease progression in acute decompensated heart failure.


Clinical Trial Description

Heart failure (HF) is an important cause of morbidity and mortality among US Veterans. Epidemiologic data points to acute decompensated heart failure (ADHF) as a leading cause of hospitalizations in the VA system. The pathophysiologic mechanisms underlying the progressive deterioration of cardiac function remain poorly understood. Autophagy is an evolutionarily conserved pathway that targets cytoplasmic contents to the lysosome for degradation in the cell. In mammals, autophagy has been classified into three different types depending on the means by which the target is delivered into lysosomes for final degradation: (i) macroautophagy, (ii) microautophagy, (iii) chaperone-mediated autophagy (CMA). Both macroautophagy and CMA may participate in degradation of damage proteins; however, only macroautophagy could clear the damage organelles in the cells. Among them, macroautophagy (thereafter and other parts of this proposal referred to as autophagy) is the best characterized. It can be induced by nutrient deprivation and various stress conditions; in these circumstances, autophagy is essential for the maintenance of cell homeostasis by its promotion of the removal of damaged components including long-live and dysfunctional proteins and damaged organelles, such as mitochondria, as well as by its provision of energy and biomolecules to cells including cardiomyocytes. Thus, autophagy is increasingly recognized to play an important role in protecting the heart against various pathological stress-induced damage and dysfunction. In contrast, it has also been proposed that autophagy may be detrimental to the heart in some specific settings. However, the precise reason for such discrepancies is poorly understood. In particularly, the regulatory mechanisms for selective control of autophagy-mediated cardiac protection or dysfunction are unclear. The therapeutic approach targeting autophagy to cardiac disease and heart failure remains to be established. An important regulatory process within the autophagy pathway is ubiquitination. Ubiquitination targets proteins for degradation. On the contrary, de-ubiquitinating proteins reverses this process. Studies have demonstrated deubiquitination to be linked to certain pathological processes, such as heart failure. Ubiquitin carboxyhydrolase L1 (UCHL1) has been identified by the co-investigator (Dr. Taixing Cui) in mouse models of pressure-overload cardiomyopathy. More data is required to identify UCHL1 as a significant marker in humans with HF. Heart failure biomarkers play an important role in heart failure care. In general, despite significant overlaps, these biomarkers are loosely arranged into the following categories: 1) myocardial stress/injury, 2) neurohormonal activation, 3) remodeling and 4) comorbidities. None of current biomarkers alone or in combination may fulfil the need regarding screening, diagnosis, prognosis and therapy guidance. Therefore, it is important to find out novel biomarkers of cardiac disease and heart failure, especially those which reflect in important pathophysiologic pathway involved in heart failure disease process and help clinical judgement for understanding diagnosis, prognosis, or management of heart failure. As a result, the novel biomarkers will supplement traditional clinical and laboratory testing to improve understanding of the complex disease processes of heart failure and possibly achieve personalized care for heart failure patients. Human studies of circulating UCHL1 have identified it as a having diagnostic or prognostic value in this pathological settings. However, whether it is applicable to cardiovascular disease has not been studied. This gap will be filled in part by this proposal. Aim: To explore the diagnostic and/or prognostic value of circulating exosomal UCH-L1 in VA HF patients. We will translate findings from animal models to bed side by a proof-of-principal study to demonstrate that circulating UCH-L1, particularly the exosomal UCH-L1 is higher during acute decompensation than when compensated in VA HF patients. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04999995
Study type Observational
Source VA Office of Research and Development
Contact Harshitha Kota, MD
Phone (803) 776-4000
Email harshitha.kota@va.gov
Status Recruiting
Phase
Start date June 1, 2021
Completion date April 1, 2025

See also
  Status Clinical Trial Phase
Recruiting NCT05654272 - Development of CIRC Technologies
Recruiting NCT05196659 - Collaborative Quality Improvement (C-QIP) Study N/A
Recruiting NCT05650307 - CV Imaging of Metabolic Interventions
Active, not recruiting NCT05896904 - Clinical Comparison of Patients With Transthyretin Cardiac Amyloidosis and Patients With Heart Failure With Reduced Ejection Fraction N/A
Completed NCT05077293 - Building Electronic Tools To Enhance and Reinforce Cardiovascular Recommendations - Heart Failure
Recruiting NCT05631275 - The Role of Bioimpedance Analysis in Patients With Chronic Heart Failure and Systolic Ventricular Dysfunction
Enrolling by invitation NCT05564572 - Randomized Implementation of Routine Patient-Reported Health Status Assessment Among Heart Failure Patients in Stanford Cardiology N/A
Enrolling by invitation NCT05009706 - Self-care in Older Frail Persons With Heart Failure Intervention N/A
Recruiting NCT04177199 - What is the Workload Burden Associated With Using the Triage HF+ Care Pathway?
Terminated NCT03615469 - Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY) N/A
Recruiting NCT05679713 - Next-generation, Integrative, and Personalized Risk Assessment to Prevent Recurrent Heart Failure Events: the ORACLE Study
Completed NCT04254328 - The Effectiveness of Nintendo Wii Fit and Inspiratory Muscle Training in Older Patients With Heart Failure N/A
Completed NCT03549169 - Decision Making for the Management the Symptoms in Adults of Heart Failure N/A
Recruiting NCT05572814 - Transform: Teaching, Technology, and Teams N/A
Enrolling by invitation NCT05538611 - Effect Evaluation of Chain Quality Control Management on Patients With Heart Failure
Recruiting NCT04262830 - Cancer Therapy Effects on the Heart
Active, not recruiting NCT06026683 - Conduction System Stimulation to Avoid Left Ventricle Dysfunction N/A
Withdrawn NCT03091998 - Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support Phase 1
Recruiting NCT05564689 - Absolute Coronary Flow in Patients With Heart Failure With Reduced Ejection Fraction and Left Bundle Branch Block With Cardiac Resynchronization Therapy
Completed NCT04549181 - Problem-Solving for Rural Heart Failure Dyads N/A