Spironolactone in Patients With Single Ventricle Heart

Congenital Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00211081
• Other study ID #: 0954-2004
• Status: Completed
• Phase: N/A
• First received: September 13, 2005
• Last updated: October 3, 2017
• Start date: November 2004
• Est. completion date: June 2008

Study information

• Verified date: October 2017
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 Patients unable to tolerate the minimum dose will be withdrawn.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:

1. At baseline

2. 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:

1. In a resting state

2. During limb ischemia

3. In response to reactive hyperemia

4. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Congenital Disorders

Intervention

Drug:
• Spironolactone (drug)
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.

Locations

Country	Name	City	State
United States	Emory Clinic	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

References & Publications (7)

Anderson TJ, Elstein E, Haber H, Charbonneau F. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol. 2000 Jan;35(1):60-6. — View Citation

Celermajer DS, Sorensen K, Ryalls M, Robinson J, Thomas O, Leonard JV, Deanfield JE. Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. J Am Coll Cardiol. 1993 Sep;22(3):854-8. — View Citation

Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. — View Citation

Celermajer DS. Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol. 1997 Aug;30(2):325-33. Review. — View Citation

Gidding SS, Rocchini AP, Moorehead C, Schork MA, Rosenthal A. Increased forearm vascular reactivity in patients with hypertension after repair of coarctation. Circulation. 1985 Mar;71(3):495-9. — View Citation

Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J. 1995 Sep;74(3):247-53. — View Citation

Yang SG, Rychik J. Mesenteric blood flow patterns: A link to protein-losing enteropathy after the Fontan operation. Circulation 1999;100-18:A3583.

Outcome

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