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Recruiting NCT03238690

LVAD Conditioning for Cardiac Recovery

No phase Interventional Heart Failure

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Controlled Cardiac Reloading through LVAD Speed Adjustment.
Who it may be relevant to
Registry conditions: Heart Failure. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Sequential Left Ventricular Assist Device (LVAD) Unloading and Conditioning to Induce Sustained Cardiac Recovery

Overview

The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a Left Ventricular Assist Device (LVAD) through applying a myocardial conditioning protocol. During myocardial conditioning, LVAD speed is reduced gradually in order to increase the work load of the heart. Multiple previous studies have shown that interventions like this may improve heart function and give patients the opportunity for a better quality of life.

Detailed description

Heart failure can be caused by various disorders, such as myocardial infarction, hypertension, viral infection, exposure to toxins, chemotherapy, or genetically transmitted muscular diseases. Regardless of the etiology, these disorders initiate ventricular remodeling, an adaptive, compensatory process which becomes progressively maladaptive and the cause of functional and clinical deterioration, eventually leading to heart failure. Local and systemic compensatory responses that initially allow surviving muscle to maintain hemodynamic function continue over time and due to this persistent compensatory over-activity the initially unaffected myocardium becomes dysfunctional. These compensatory responses to an abnormal cardiac load or myocardial injury involve several pathophysiological adaptations in the cardiac structure at the genetic, molecular, cellular, and tissue levels. Furthermore, left ventricular pressure and volume overload has shown to alter metabolic substrate utilization, decrease mitochondrial function and reduce energy production in the failing heart.

Mechanical circulatory support with LVAD has become a standard bridge to cardiac transplantation, and has also been approved in the United States as permanent (destination) therapy for selected patients presenting with end-stage heart failure. Clinical experience with LVAD support has shown that it can reverse the complex process of chronic left ventricular remodeling to a point where a subset of patients could be weaned from the device after restoration of basic cardiac function. LVAD-induced mechanical unloading of the failing heart leads to reduced mitochondrial density, structure and function, and interventions that enhance mitochondrial biogenesis, function and structure, such as controlled cardiac reloading may enhance LVAD-induced myocardial reverse remodeling and cardiac recovery. This study is designed to investigate gradual reduction in LVAD speed within the range defined by the assist device manufacturer's manual as appropriate for regular clinic use, to determine the effect on reverse remodeling and myocardial recovery in end-stage heart failure patients.

Interventions

  • Device Controlled Cardiac Reloading through LVAD Speed Adjustment
    LVAD speed is reduced at a fixed rate according to the particular LVAD device model implanted. LVAD speed reduction adjustments will be performed at visits occurring every 2 - 3 weeks, up to a total of 8 visits. Reduction of LVAD speed will continue until the soonest of: minimum operating setting as recommended in the LVAD Operator's manual is reached; the minimum setting tolerated by the subject is reached; the subject completes 8 visits; or until the subject receives a heart transplant.

Primary outcome measures

  • Change in Left Ventricular Ejection Fraction (LVEF) [Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant]
Secondary outcome measures (12)
  • Change in Left Ventricular End Diastolic Diameter (LVEDD) [Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant]
  • Change in Left Ventricular End Systolic Diameter (LVESD) [Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant]
  • Change in Left Ventricular End Diastolic Volume (LVEDV) [Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant]
  • Change in Left Ventricular End Systolic Volume (LVESV) [Time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant]
  • Change in heart tissue Glucose 1-phosphate levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Glucose 6-phosphate levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Pyruvate levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Lactic Acid levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Acetyl Coenzyme A levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Glucose Transporter 1 (GLUT1) levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Glucose Transporter 1 (GLUT1) messenger ribonucleic acid (mRNA) levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]
  • Change in heart tissue Glucose Transporter 4 (GLUT4) levels [Time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)]

Eligibility criteria

Inclusion criteria

  • Diagnosed with heart failure undergoing LVAD implantation as a bridge to transplant
  • Enrolled in the Effects of Mechanical Unloading on Myocardial Function and Structure study (IRB 30622)

Exclusion criteria

  • Neither the subject nor the subject's representative is willing to provide written consent for participation
  • Subjects with adverse events leading to hospitalization during the optimum unloading phase are excluded from participation in the controlled reloading phase

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 1 center
  • University of Utah — Salt Lake City

Publications

  • George RS, Sabharwal NK, Webb C, Yacoub MH, Bowles CT, Hedger M, Khaghani A, Birks EJ. Echocardiographic assessment of flow across continuous-flow ventricular assist devices at low speeds. J Heart Lung Transplant. 2010 Nov;29(11):1245-52. doi: 10.1016/j.healun.2010.05.032. Epub 2010 Aug 5. PMID 20688540
  • Healy AH, Koliopoulou A, Drakos SG, McKellar SH, Stehlik J, Selzman CH. Patient-controlled conditioning for left ventricular assist device-induced myocardial recovery. Ann Thorac Surg. 2015 May;99(5):1794-6. doi: 10.1016/j.athoracsur.2014.07.058. PMID 25952209
  • Frazier OH, Baldwin AC, Demirozu ZT, Segura AM, Hernandez R, Taegtmeyer H, Mallidi H, Cohn WE. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015 Jun;34(6):766-72. doi: 10.1016/j.healun.2014.09.015. Epub 2014 Sep 28. PMID 25447571

Identifiers

NCT: NCT03238690 · IRB_00095106

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗