Effect of Aldosterone on Energy Starvation in Heart Failure

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00574119
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 55
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

We plan to study the concept of "energy starvation" in heart failure by evaluation of patients with nonischemic dilated cardiomyopathy (NIDCM) (heart failure with reduced heart pump function due to causes other than heart attack). We will use a combination of positron emission tomography and magnetic resonance imaging to study metabolism, anatomy, function, blood flow and efficiency, before and after 6 months' treatment with the drug spironolactone which blocks the deleterious effects of the hormone aldosterone on the myocardium (heart muscle).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Nonischemic Dilated Cardiomyopathy	Drug: spironolactone	Phase 4

Detailed Description

Preliminary results showed reduced subendocardial myocardial perfusion reserve in NIDCM compared to normal subjects, and that the degree of impaired perfusion reserve was related to the oxidative metabolic rate as measured by positron emission tomography.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Effect of Aldosterone on Energy Starvation in Heart Failure
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Results with spironolactone patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone.	Drug: spironolactone; spironolactone 50 mg daily for 6 months; Other Names: Aldactone

Outcome Measures

Primary Outcome Measures

1. Left Ventricular Work-metabolic Index (WMI) at Baseline [baseline]

   WMI=[left ventricular stroke work/decay rate of 11C-acetate]

2. Left Ventricular Work-metabolic Index (WMI) at 6 Months [6 months]

   WMI=[left ventricular stroke work/decay rate of 11C-acetate]

3. Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at Baseline [baseline]

   MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope.

4. Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 6 Months [6 months]

   MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope.

5. Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging [baseline and 6 months]

   T1=left ventricular relaxation rate on magnetic resonance imaging, which is correlated with interstitial fibrosis.

Secondary Outcome Measures

1. 6 Minute Walk Test (6MWT) at Baseline [baseline]

   6MWT assesses distance walked over 6 minutes

2. 6 Minute Walk Test (6MWT) at 6 Months [6 months]

   6MWT assesses distance walked over 6 minutes

3. Minnesota Living With Heart Failure Questionnaire,at Baseline [baseline]

   The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure.

4. Minnesota Living With Heart Failure Questionnaire.at 6 Months [6 months]

   The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years or older

• Nonischemic dilated cardiomyopathy

• Left ventricular ejection fraction 35% or less

• Stable heart failure symptoms

• Able to undergo both positron emission tomography and magnetic resonance imaging with gadolinium

• Able to tolerate treatment with spironolactone

Exclusion Criteria:

• Serum potassium >5.0

• Serum creatinine >2.5

• Contraindications to magnetic resonance imaging such as internal cardioverter-defibrillator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt Heart and Vascular Institute	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: Marvin W Kronenberg, MD, Vanderbilt University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 22, 2011

More Information

Publications

None provided.

• Responsible Party: Marvin W. Kronenberg, M.D., Professor of Medicine and Radiology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00574119
• Other Study ID Numbers: IRB 070824
• First Posted: Dec 17, 2007
• Last Update Posted: Jun 18, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Marvin W. Kronenberg, M.D., Professor of Medicine and Radiology, Vanderbilt University: heart failure; positron emission tomography; magnetic resonance imaging; myocardial energetics; myocardial perfusion
• Additional relevant MeSH terms: Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated; Starvation; Spironolactone

Study Results

Participant Flow

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Period Title: Overall Study
STARTED	16
COMPLETED	12
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Overall Participants	15
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	52
Sex: Female, Male (Count of Participants)
Female	5 33.3%
Male	10 66.7%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Left Ventricular Work-metabolic Index (WMI) at Baseline
Description	WMI=[left ventricular stroke work/decay rate of 11C-acetate]
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

12 patients completed study

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [(x10^6), mL x mm Hg/m^2]	7.4

2. Primary Outcome

Title	Left Ventricular Work-metabolic Index (WMI) at 6 Months
Description	WMI=[left ventricular stroke work/decay rate of 11C-acetate]
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

12 patients completed study

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [(x10^6), mL x mm Hg/m^2]	5.4

3. Primary Outcome

Title	Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at Baseline
Description	MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Mean (Inter-Quartile Range) [MPRI]	1.72

4. Primary Outcome

Title	Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 6 Months
Description	MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Mean (Inter-Quartile Range) [MPRI]	1.80

5. Primary Outcome

Title	Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging
Description	T1=left ventricular relaxation rate on magnetic resonance imaging, which is correlated with interstitial fibrosis.
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Mean (Standard Deviation) [msec]	6 (37)

6. Secondary Outcome

Title	6 Minute Walk Test (6MWT) at Baseline
Description	6MWT assesses distance walked over 6 minutes
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [meters]	521

7. Secondary Outcome

Title	6 Minute Walk Test (6MWT) at 6 Months
Description	6MWT assesses distance walked over 6 minutes
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [meters]	542

8. Secondary Outcome

Title	Minnesota Living With Heart Failure Questionnaire,at Baseline
Description	The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [score on a scale]	54

9. Secondary Outcome

Title	Minnesota Living With Heart Failure Questionnaire.at 6 Months
Description	The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
Measure Participants	12
Median (Inter-Quartile Range) [score on a scale]	22

Adverse Events

Time Frame	6 months
Arm/Group Title	Results With Spironolactone
Arm/Group Description	patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. spironolactone: spironolactone 50 mg daily for 6 months
All Cause Mortality
	Results With Spironolactone
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Serious Adverse Events
	Results With Spironolactone
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Results With Spironolactone
	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)
Cardiac disorders
pacemaker insertion	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
shortness of breath	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.