Spironolactone in Patients With Single Ventricle Heart

Study Overview
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Brief Summary
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Ultrasound is a technique that can provide images of the blood vessels such as arteries. The size of the arteries, such as the main blood vessel in the arm, can change under different conditions. Using ultrasound we can see how arteries change with movement or even drugs. We want to use ultrasound to see how blood vessels look in patients with Congestive Heart Failure (CHF) and to also see how a drug called Spironolactone, commonly prescribed for patients with this disease, effects blood vessel function in patients with congestive heart failure. This information may be used to change the standard of care for patients with heart failure especially if we show that Spironolactone has a positive effect on vessel function in patients with CHF.

Detailed Description
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Spironolactone The starting dose of spironolactone is 1 mg/kg/day. After two weeks this dose will be doubled to the same maximum dose (2/mg/kg/day) as in RALES. If side effects occur or plasma urea and electrolytes became deranged the dose will be halved. Patients unable to tolerate the minimum dose will be withdrawn. Measurement of serum electrolytes will occur at baseline, at two weeks, and at time of repeat evaluation. Endothelial Function Subjects with single ventricle will have an evaluation of endothelial function: At baseline On spironolactone- 4-5 weeks after initial study. Imaging protocol: The diameter of the brachial artery will be measured from two-dimensional ultrasound images, using a 12 MHz linear array transducer and an Accuson Sequoia system (Accuson, Mountainview, California). Measurements of the brachial artery will be obtained: In a resting state During limb ischemia In response to reactive hyperemia At rest Reactive hyperemia will be induced by inflating a standard blood pressure cuff to 50 mm Hg above the systolic blood pressure for 4.5 minutes and then deflating the cuff. After data collection, the DICOM-formatted images will be transferred to a PC for investigator-blinded measurement of brachial artery diameter using image analysis software (Brachial Tools 3.1, Medical Imaging Applications, Iowa). Measurement of prognostic markers: Blood samples Plasma beta-type natriuretic peptide, form assay, TNF alpha and a Cytokine panel will be drawn at base line and at the final 4-5 week visit for this study. Samples will be collected between 11 am and 1 pm after 30 minutes' supine rest. The samples will be centrifuged and plasma stored at -70°C (peptides) or -20°C (other samples). Plasma [beta]-type natriuretic peptide (BNP) samples will be collected into EDTA and aprotonin and measured by radioimmunoassay 6-minute walk test. A 6-minute walk test will be performed at the first visit and the last visit. During this test, signs and symptoms will be recorded (i.e. chest pain and shortness of breath) to determine toleration of daily activity. A doctor or nurse will conduct this test and the patient will be provided the opportunity to stop or rest if symptoms become severe. Outcome measures The primary outcome measure will be the change in flow mediated dilation (during reactive hyperemia). This will be expressed as a percentage. Secondary outcome measures will include changes in BNP, Form assay, TNF alpha, Cytokine panels and the 6-minute walk test. Statistical analysis We and others have previously shown that asymptomatic patients with the Fontan operation have a mean flow-mediated dilation of approximately 4% compared to 8-9% in controls. In order to detect a 25% change in FMD, with a power of 0.80, the current study would require a patient population of 13 cases. There are currently over 40 patients with single ventricle who are followed in the adult congenital clinic at Emory University. We plan on enrolling 20 patients into this study.

Official Title
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Impact of Spironolactone on Endothelial Function in Patients With Single Ventricle Heart

Conditions
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Congenital Disorders

Intervention / Treatment
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* Drug: Spironolactone (drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single Ventricle Subjects >17 years have undergone Fontan Procedure Exclusion Criteria: History of smoking Diabetes mellitus Renal failure (serum creatinine > 2.5 mg/dl) Recovering spironolactone for maintenance therapy History of hyperkalemia (serum potassium> 5.5 mEq/L)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br> | Drug: Spironolactone (drug)<br>* 1 mg/kg/day; afer 2 weeks doubled to 2/mg/kg/day. Patient's with endothelium-dependent brachial artery vasodilation and single-ventricle should show improvement within 4-8 weeks. Patients and their labs who are receiving Spironolactone will be followed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flow Mediated Dilation | Flow-mediated dilation of the brachial artery will be measured using high-resolution ultrasound. Arterial diameter will be measured above the small cavity in the elbow joint from ultrasound images at rest in response to an increase in blood flow to the area. | Baseline, Post-Intervention (4 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-Reactive Protein Level | The normal reference range for C-reactive protein is as follows: CRP: 0-10mg/L | Baseline, Post-Intervention (4 Weeks) | 
| Interleukin-6 (IL-6) Level | The normal result for IL-6 for Interleukin 6 is < 5pg/ml. | Baseline, Post-Intervention (4 Weeks) | 
| Interleukin 1 Beta (IL1b) Level | The normal result for IL1b is <3.9 pg/mL. | Baseline, Post-Intervention (4 Weeks) | 
| Interleukin-10 (IL10) Level | The normal result for IL-10 for Interleukin 10 is < 18pg/ml. | Baseline, Post-Intervention (4 Weeks) | 
| Tumor Necrosis Factor-Alpha (TNF-a) Level | The normal result for TNF-a is <5.6 pg/mL. | Baseline, Post-Intervention (4 Weeks) | 
| Change in 6 Minute Walk Test Score |  | Baseline, Post-Intervention (4 Weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital Heart Disease, Spironolactone, >17 years old, undergone Fontan procedure, endothelial function