Spironolactone in Patients With Single Ventricle Heart
Primary Purpose
Congenital Disorders
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Spironolactone (drug)
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Disorders focused on measuring Congenital Heart Disease, Spironolactone, >17 years old, undergone Fontan procedure, endothelial function
Eligibility Criteria
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)
Sites / Locations
- Emory Clinic
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open Label
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
C-Reactive Protein Level
The normal reference range for C-reactive protein is as follows: CRP: 0-10mg/L
Interleukin-6 (IL-6) Level
The normal result for IL-6 for Interleukin 6 is < 5pg/ml.
Interleukin 1 Beta (IL1b) Level
The normal result for IL1b is <3.9 pg/mL.
Interleukin-10 (IL10) Level
The normal result for IL-10 for Interleukin 10 is < 18pg/ml.
Tumor Necrosis Factor-Alpha (TNF-a) Level
The normal result for TNF-a is <5.6 pg/mL.
Change in 6 Minute Walk Test Score
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00211081
Brief Title
Spironolactone in Patients With Single Ventricle Heart
Official Title
Impact of Spironolactone on Endothelial Function in Patients With Single Ventricle Heart
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed 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:
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Disorders
Keywords
Congenital Heart Disease, Spironolactone, >17 years old, undergone Fontan procedure, endothelial function
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open Label
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Spironolactone (drug)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Flow Mediated Dilation
Description
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.
Time Frame
Baseline, Post-Intervention (4 Weeks)
Secondary Outcome Measure Information:
Title
C-Reactive Protein Level
Description
The normal reference range for C-reactive protein is as follows: CRP: 0-10mg/L
Time Frame
Baseline, Post-Intervention (4 Weeks)
Title
Interleukin-6 (IL-6) Level
Description
The normal result for IL-6 for Interleukin 6 is < 5pg/ml.
Time Frame
Baseline, Post-Intervention (4 Weeks)
Title
Interleukin 1 Beta (IL1b) Level
Description
The normal result for IL1b is <3.9 pg/mL.
Time Frame
Baseline, Post-Intervention (4 Weeks)
Title
Interleukin-10 (IL10) Level
Description
The normal result for IL-10 for Interleukin 10 is < 18pg/ml.
Time Frame
Baseline, Post-Intervention (4 Weeks)
Title
Tumor Necrosis Factor-Alpha (TNF-a) Level
Description
The normal result for TNF-a is <5.6 pg/mL.
Time Frame
Baseline, Post-Intervention (4 Weeks)
Title
Change in 6 Minute Walk Test Score
Time Frame
Baseline, Post-Intervention (4 Weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William T Mahle, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Arshed Quyyumi, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wendy M Book, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael E McConnell, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
1359209
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. doi: 10.1016/0140-6736(92)93147-f.
Results Reference
background
PubMed Identifier
7547018
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. doi: 10.1136/hrt.74.3.247.
Results Reference
background
PubMed Identifier
9247501
Citation
Celermajer DS. Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol. 1997 Aug;30(2):325-33. doi: 10.1016/s0735-1097(97)00189-7.
Results Reference
background
PubMed Identifier
8354824
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. doi: 10.1016/0735-1097(93)90203-d.
Results Reference
background
PubMed Identifier
10636260
Citation
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. doi: 10.1016/s0735-1097(99)00537-9.
Results Reference
background
PubMed Identifier
3971523
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. doi: 10.1161/01.cir.71.3.495.
Results Reference
background
Citation
Yang SG, Rychik J. Mesenteric blood flow patterns: A link to protein-losing enteropathy after the Fontan operation. Circulation 1999;100-18:A3583.
Results Reference
background
Learn more about this trial
Spironolactone in Patients With Single Ventricle Heart
We'll reach out to this number within 24 hrs