Cardiac Resynchronization and Iodine Meta-Iodobenzylguanidine (MIBG) Imaging

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Mayo Clinic
Sponsor:
Collaborator:
GE Healthcare
Information provided by (Responsible Party):
Yong-Mei Cha, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01522378
First received: January 27, 2012
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

Congestive heart failure (CHF) affects nearly 5 million Americans and claims more than 300,000 lives annually. A primary pathophysiologic mechanism in this deadly syndrome is an abnormally enhanced sympathetic nervous system that results in profound peripheral vasoconstriction, attenuated cardiovascular reflexes, higher susceptibility to ventricular arrhythmias, and sudden cardiac death. The reduction in mortality and morbidity in CHF by pharmacologic neurohumoral antagonists such as beta-receptor inhibitor and angiotensin II-converting enzyme (ACE) inhibitor has taught us that regulation of the impaired neurohumoral axis is important for improving clinical outcome. In addition, an emerging nonpharmacologic approach, cardiac resynchronization therapy (CRT), has shown promise for improving symptoms and quality of life in patients with New York Heart Association (NYHA) functional class III or IV and intraventricular conduction delay. However, despite significant advances in CHF treatment in the past two decades, a gap remains between clinical outcome and the mechanisms of the protective effects of these modern therapies.

CHF is associated with increased concentrations of circulating norepinephrine (NE), down-regulation of adrenergic nerve terminals, and abnormal NE reuptake. The suppression of cardiac sympathetic nerve endings could be reversed by CRT, a novel anti-heart failure therapy, by rebalance cardiac sympathetic activity, and improve cardiac function in patients with heart failure.


Condition Intervention
Congestive Heart Failure
Drug: 123 iodine metaiodobenzylguanidine

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cardiac Resynchronization and MIBG Imaging

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Changes in 123I-MIBG parameters [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]
    changes in 123I-MIBG parameters with cardiac performance including LVEF, SV, LV and LA dimension, distance of 6-minute walk, NYHA class, and ventricular arrhythmic burden


Secondary Outcome Measures:
  • submaximal exercise gas exchange [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]
    Subjects will perform simplified low intensity cardiopulmonary exercise testing in our laboratory where they breathe for 1 min at rest, perform graded step exercise, increasing from 60,90,120 steps per minute until achieving a perceived exertion of 12-14 on the 6-20 Borg scale. This will be followed by a 1 min recovery. Subjects will be instrumented with ECG, pulse oximeter and breathe on a mouthpiece where ventilation, oxygen and carbon dioxide are measured continuously to calculate the desired parameters of VE/VCO2, PetCO2 and O2Pulse on a breath by breath basis.

  • Autonomic function [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]
    In addition to the simplified submaximal step test, subjects will also perform a simplified battery of tests for autonomic function. This will include supine to upright measures of heart rate and heart rate variability (HRV), paced breathing (slow to faster frequencies) as well as tracking HRV and responses to the increased metabolic demands of exercise and into recovery.


Estimated Enrollment: 106
Study Start Date: February 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 123 iodine metaiodobenzylguanidine
    10 mCi (370 MBq)
    Other Name: AdreView
Detailed Description:

The Specific Aim #1 of this study is to assess, with 123iodine metaiodobenzylguanidine (123I-MIBG imaging), whether CRT rebalances and improves the integrity and function of sympathetic nerve terminals in the failing myocardium. The study will test the hypothesis that resynchronization of biventricular contractility attenuates excessive sympathetic drive, and improves autonomic function and cardiac performance.

The Specific Aim #2 of this study is to determine the relationship between 123I-MIBG labeling of sympathetic activity and physiological measures of cardiopulmonary and autonomic function. This aim is to test the hypothesis that impaired cardiac sympathetic activity, determined by 123I-MIBG imaging will be associated with poorer submaximal exercise gas exchange (higher ventilation - CO2 slopes, low end tidal CO2, reduced oxygen pulse and a more rapid frequency response) as well as reduced heart rate power spectral frequencies, a blunted response to positional changes and a delayed heart rate recovery.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: Indications for Biv-ICD implantation

  1. Chronic moderate to severe CHF (NYHA class II or IV)
  2. Left ventricular ejection fraction (LVEF) of 35% or less
  3. QRS duration of 120 ms or more
  4. On optimized anti-heart failure medical regimen
  5. Meet one of the following indications for ICD

    • Survivors of cardiac arrest due to ventricular fibrillation (VF) or ventricular tachycardia (VT) or spontaneous sustained VT
    • Nonsustained VT with coronary disease, prior myocardial infarction, LVEF 35% or less, and inducible VF or sustained VT at electrophysiologic study
    • LVEF of 30% or less with severe coronary artery disease

Exclusion criteria:

  1. Patient condition is unstable
  2. Patient is unable to give informed consent
  3. Not feasible for patient to be followed at Mayo Clinic
  4. Female in pregnancy and breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01522378

Contacts
Contact: Celeste Koestler, RN 507-255-2200 koestler.celeste@mayo.edu
Contact: Peggy Weivoda 507-255-8923 weivoda.peggy@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Celeste M Koestler, RN    507-255-2200    koestler.celeste@mayo.edu   
Principal Investigator: Yong-Mei Cha, MD         
Sponsors and Collaborators
Mayo Clinic
GE Healthcare
Investigators
Principal Investigator: Yongmei Cha, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Yong-Mei Cha, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01522378     History of Changes
Other Study ID Numbers: 11-006296
Study First Received: January 27, 2012
Last Updated: June 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
cardiac resynchronization therapy

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Iodine
3-Iodobenzylguanidine
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014