Effect of Aldosterone on Energy Starvation in Heart Failure

NCT00574119 | Completed Phase 4 Results

• 1 other identifier: IRB 070824
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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).

Conditions

Heart Failure; Nonischemic Dilated Cardiomyopathy

Keywords

heart failure; positron emission tomography; magnetic resonance imaging; myocardial energetics; myocardial perfusion

Outcome Measures

Primary Outcomes (5)

• Left Ventricular Work-metabolic Index (WMI) at Baseline

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

  baseline

• Left Ventricular Work-metabolic Index (WMI) at 6 Months

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

  6 months

• Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at 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.

  baseline

• Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 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.

  6 months

• Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging

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

  baseline and 6 months

Secondary Outcomes (4)

• 6 Minute Walk Test (6MWT) at Baseline

  baseline

• 6 Minute Walk Test (6MWT) at 6 Months

  6 months

• Minnesota Living With Heart Failure Questionnaire,at Baseline

  baseline

• Minnesota Living With Heart Failure Questionnaire.at 6 Months

  6 months

Study Arms (1)

Results with spironolactone

EXPERIMENTAL

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

Interventions

spironolactone DRUG

spironolactone 50 mg daily for 6 months

Also known as: Aldactone

Results with spironolactone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Serum potassium \>5.0
• Serum creatinine \>2.5
• Contraindications to magnetic resonance imaging such as internal cardioverter-defibrillator.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Heart and Vascular Institute

Nashville, Tennessee, 37232, United States

Location

Related Publications (5)

• Lawson MA, Hansen DE, Gupta DK, Bell SP, Adkisson DW, Mallugari RR, Sawyer DB, Ooi H, Kronenberg MW. Modification of ventriculo-arterial coupling by spironolactone in nonischemic dilated cardiomyopathy. ESC Heart Fail. 2021 Apr;8(2):1156-1166. doi: 10.1002/ehf2.13161. Epub 2021 Jan 5.

  PMID: 33403831 DERIVED

• Bradham WS, Bell SP, Huang S, Harrell FE Jr, Adkisson DW, Lawson MA, Sawyer DB, Ooi H, Kronenberg MW. Timing of Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy. Am J Med Sci. 2018 Sep;356(3):262-267. doi: 10.1016/j.amjms.2018.06.003. Epub 2018 Jun 8.

  PMID: 30286821 DERIVED

• Lawson MA, Bell SP, Adkisson DW, Wang L, Ooi H, Sawyer DB, Kronenberg MW. High reproducibility of adenosine stress cardiac MR myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy. BMJ Open. 2014 Dec 16;4(12):e005984. doi: 10.1136/bmjopen-2014-005984.

  PMID: 25515841 DERIVED

• Bell SP, Adkisson DW, Lawson MA, Wang L, Ooi H, Sawyer DB, Kronenberg MW. Antifailure therapy including spironolactone improves left ventricular energy supply-demand relations in nonischemic dilated cardiomyopathy. J Am Heart Assoc. 2014 Aug 27;3(4):e000883. doi: 10.1161/JAHA.114.000883.

  PMID: 25164945 DERIVED

• Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. J Card Fail. 2013 Dec;19(12):802-10. doi: 10.1016/j.cardfail.2013.10.010. Epub 2013 Oct 29.

  PMID: 24331202 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Marvin W. Kronenberg,M.D.
• Organization: Vanderbilt University School of Medicine

marvin.w.kronenberg@vumc.org

615 936-7437

Study Officials

• Marvin W Kronenberg, MD

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Radiology

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 17, 2007
• Study Start: December 1, 2007
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 18, 2019
• Results First Posted: June 18, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)