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L-Arginine and Spironolactone Trial in Dialysis-Dependent ESRD

Information source: Brigham and Women's Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: End Stage Renal Disease; Hemodialysis

Intervention: Spironolactone (Drug); L-arginine (Dietary Supplement); Placebo (Drug)

Phase: Phase 4

Status: Withdrawn

Sponsored by: Brigham and Women's Hospital


Cardiovascular disease is the primary cause of death in patients with end stage renal disease (ESRD). New research suggests that the high risk of death may be partly due to high levels of fibrosis and a loss of small blood vessels in the heart of patients with dialysis-dependent ESRD. This study is designed to compare the effects of two different drugs, spironolactone and L-arginine, with placebo on structure and function of the heart in individuals with dialysis-dependent ESRD.

Clinical Details

Official title: A Randomized, Controlled Trial of L-arginine and Spironolactone in Dialysis-dependant End Stage Renal Disease

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Change in coronary Flow Reserve (PET)

Change in left ventricular diastolic function

Secondary outcome:

Association between coronary flow reserve (CFR) and tissue doppler index (E')

Change in resting myocardial blood flow

Change in left ventricular mass index

Change in coronary vascular resistance

Association between change in coronary flow reserve (CFR) and change in diastolic function-tissue doppler index (E')

Change in early diastolic function (E')

Combined cardiovascular safety

Cardiovascular death



Change in early coronary flow reserve

Change in hyperemic myocardial blood flow

Detailed description: We hypothesize that that abnormalities in aldosterone and nitric oxide (NO) homeostasis contribute to the progression of microvascular disease and myocardial fibrosis in ESRD and that agents designed to restore normal aldosterone and NO homeostasis will improve microvascular and diastolic cardiac function in the heart of individuals with dialysis dependent ESRD. We will test 2 specific agents: The mineralocorticoid receptor blocker spironolactone; and L-arginine, an agent which improves NO bioavailability. Two specific aims will be addressed using a prospective, double-blinded, 2x2 factorial trial in dialysis dependent patients with ESRD. Subjects will be randomized to placebo, spironolactone plus placebo, L-arginine plus placebo, or combination spironolactone and L-arginine therapy. Diastolic cardiac function will be assessed using tissue Doppler index (TDI) determined mitral annular velocities (E') on LV echocardiography, and microvascular supply will be assessed using CFR—the ratio of hyperemic to resting myocardial blood flow—measured by positron emission tomography (PET) scans at baseline, 2 weeks and after 9 months of randomized therapy. This randomized trial of spironolactone and L-arginine will provide important data about the contributions of aldosterone and NO to the pathogenesis of cardiovascular disease in ESRD, will demonstrate the therapeutic potential of L-arginine and spironolactone as as targeted cardiovascular therapies for use in ESRD, and will provide important insights into the underlying pathophysiology of cardiovascular disease in ESRD. The results generated will provide the data needed to design large-scale trials testing whether spironolactone or L-arginine can improve mortality or cardiovascular outcomes in ESRD.


Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.


Inclusion Criteria:

- Chronic dialysis therapy for End Stage Renal Disease

- Age 21-85

Exclusion Criteria:

- Hyperkalemia requiring unscheduled dialysis within 3 months

- Pre-dialysis potassium ≥6. 5 meq/L within 3 months

- Hypotension defined as SBP <100

- Recurrent intra-dialytic hypotension defined as recurrent cramping, light-headedness,

or hypotension requiring infusion of saline or other intervention or otherwise limiting ability to achieve dry weight. Or SBP <80

- History of myocardial infarction

- History of coronary artery bypass surgery

- Non revascularized coronary disease >90%

- Mitral valve repair or replacement

- Severe mitral valve disease

- Renal transplant expected within 9 months

- Expected survival < 9 months

- Pregnant

- Prisoners

- Unable to provide consent

- Allergy to spironolactone or L-arginine

- Digitalis use

- 1st or 2nd degree heart block

Locations and Contacts

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

Brigham & Women's Hospital, Boston, Massachusetts 02120, United States

Massachusetts General Hospital, Boston, Massachusetts 021114, United States

Additional Information

Starting date: September 2013
Last updated: January 6, 2015

Page last updated: August 23, 2015

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