Cardiac Resynchronization and Iodine Meta-Iodobenzylguanidine (MIBG) Imaging

• ClinicalTrials.gov Identifier: NCT01522378
• Recruitment Status: Terminated
• First Posted: January 31, 2012
• Last Update Posted: April 26, 2017
• Sponsor: Mayo Clinic
• Collaborator: GE Healthcare
• Information provided by (Responsible Party): Yong-Mei Cha, Mayo Clinic

Tracking Information

• First Submitted Date: January 27, 2012
• First Posted Date: January 31, 2012
• Last Update Posted Date: April 26, 2017
• Study Start Date: February 2012
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2017)

Change in 123I-MIBG parameters [ Time Frame: baseline, 6 months ]

changes in 123I-MIBG parameters with cardiac performance including LVEF, stroke volume (SV), left ventricle (LV) and left atrium (LA) dimension, distance of 6-minute walk, NYHA class, and ventricular arrhythmic burden

Original Primary Outcome Measures (submitted: January 30, 2012)

Changes in 123I-MIBG parameters [ Time Frame: baseline & 6 months ]

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

Current Secondary Outcome Measures (submitted: April 24, 2017)

• Change in submaximal exercise gas exchange [ Time Frame: baseline, 6 months ]
  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 ventilatory efficiency (VE/VCO2), PetCO2 and oxygen pulse (O2Pulse) on a breath by breath basis.
• Change in Autonomic function [ Time Frame: baseline, 6 months ]
  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.

Original Secondary Outcome Measures (submitted: January 30, 2012)

• submaximal exercise gas exchange [ Time Frame: baseline & 6 months ]
  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 ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cardiac Resynchronization and Iodine Meta-Iodobenzylguanidine (MIBG) Imaging
• Official Title: Cardiac Resynchronization and MIBG Imaging
• Brief Summary: Subjects were recruited if their healthcare provider decided that they needed treatment with a special Internal Cardiac Defibrillator (ICD) called a biventricular ICD. The investigators did this study to see if part of the nerve organ, called the sympathetic nervous system, may be responsible for the improvement seen in patients that receive biventricular pacing. The investigators had three ways to measure sympathetic nervous activity: 1) by using a special blood sample, 2) by monitoring heart rhythm, and 3) by performing a special heart scan.

Detailed Description

The Specific Aim #1 of this study is to assess, with 123iodine metaiodobenzylguanidine (123I-MIBG imaging), whether cardiac resynchronization therapy (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 - carbon dioxide (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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Congestive Heart Failure

Intervention

Drug: 123 iodine metaiodobenzylguanidine

10 millicurie (mCi) (370 MBq)

Other Name: AdreView

Study Arms

Experimental: Biv-ICD

Subjects will be imaged with 123 iodine metaiodobenzylguanidine.

Intervention: Drug: 123 iodine metaiodobenzylguanidine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 2, 2016): 14
• Original Estimated Enrollment (submitted: January 30, 2012): 106
• Actual Study Completion Date: February 2016
• Actual Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria: Indications for Biv-ICD implantation

1. Chronic moderate to severe congestive heart failure (CHF) (NYHA class II or IV)
2. Left ventricular ejection fraction (LVEF) of 35% or less
3. Q wave, R wave and S wave (QRS complex) 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01522378
• Other Study ID Numbers: 11-006296
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Yong-Mei Cha, Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: GE Healthcare

Investigators

• Principal Investigator: Yongmei Cha, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: April 2017