L-Arginine and Spironolactone Trial in Dialysis-Dependent ESRD

NCT01855334 | Withdrawn Phase 4 DMC

• 1 other identifier: 1R01DK096189
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

End Stage Renal Disease; Hemodialysis

Keywords

Dialysis; ESRD; Cardiovascular disease; spironolactone; L-arginine; myocardial perfusion; coronary flow reserve; diastolic function

Outcome Measures

Primary Outcomes (2)

• Change in coronary Flow Reserve (PET)

  Coronary flow reserve will be measured using rest and stress 13N ammonia myocardial positron emission tomography (PET) at baseline and 9 months

  Between baseline and 9 months

• Change in left ventricular diastolic function

  Left ventricular diastolic function will be measured using mitral annular E' on tissue doppler index echocardiography at baseline and 9 months

  Between baseline and 9 months

Secondary Outcomes (12)

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

  Baseline

• Change in resting myocardial blood flow

  Between baseline and 9 months

• Change in left ventricular mass index

  Between baseline and 9 months

• Change in coronary vascular resistance

  Between 0 and 9 months

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

  Between baseline and 9 months

Study Arms (4)

Spironolactone + Placebo

EXPERIMENTAL

Spironolactone 25 mg by mouth daily + Placebo L-arginine-liquid formulation by mouth 3 times daily

Drug: Spironolactone; Drug: Placebo

Double Placebo

PLACEBO COMPARATOR

Placebo spironolactone-1 tablet by mouth daily + Placebo L-arginine liquid formulation by mouth 3 times daily

Drug: Placebo

Spironolactone + L-arginine

EXPERIMENTAL

Spironolactone 25 mg daily + L-arginine 3 grams orally 3 times daily

Drug: Spironolactone; Dietary Supplement: L-arginine

L-arginine + Placebo

EXPERIMENTAL

L-arginine 3 grams by mouth 3 times daily + Placebo spironolactone 1 tablet by mouth daily

Dietary Supplement: L-arginine; Drug: Placebo

Interventions

Spironolactone DRUG

Also known as: Aldactone

Spironolactone + L-arginine; Spironolactone + Placebo

L-arginine DIETARY_SUPPLEMENT

L-arginine + Placebo; Spironolactone + L-arginine

Placebo DRUG

Double Placebo; L-arginine + Placebo; Spironolactone + Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic dialysis therapy for End Stage Renal Disease
• Age 21-85

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Massachusetts General Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Joslin Diabetes Center: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 021114, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.

  PMID: 33586138 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Cardiovascular Diseases

Interventions

Spironolactone; Arginine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 16, 2013
• Study Start: September 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

US (3)