Congenital DisordersNCT00211081
Spironolactone in Patients With Single Ventricle Heart
A study testing Spironolactone (drug) in people with Congenital Disorders, run by Emory University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congenital Disorders
- What is being tested?
- Spironolactone (drug)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2004to Jun 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Single Ventricle Subjects
- >17 years
- have undergone Fontan Procedure
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Spironolactone on Endothelial Function in Patients With Single Ventricle Heart
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.
Read the 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.
- Conditions
- Congenital Disorders
- Being tested
- Spironolactone (drug)
- Keywords
- Congenital Heart Disease, Spironolactone, >17 years old, undergone Fontan procedure, endothelial function
- Medical subject headings
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spironolactone (drug)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.
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | Not described Receives: Drug: Spironolactone (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Post-Intervention (4 Weeks)
Secondary outcomes (6)
C-Reactive Protein Level
The normal reference range for C-reactive protein is as follows: CRP: 0-10mg/L
Measured: Baseline, Post-Intervention (4 Weeks)
Interleukin-6 (IL-6) Level
The normal result for IL-6 for Interleukin 6 is < 5pg/ml.
Measured: Baseline, Post-Intervention (4 Weeks)
Interleukin 1 Beta (IL1b) Level
The normal result for IL1b is <3.9 pg/mL.
Measured: Baseline, Post-Intervention (4 Weeks)
Interleukin-10 (IL10) Level
The normal result for IL-10 for Interleukin 10 is < 18pg/ml.
Measured: Baseline, Post-Intervention (4 Weeks)
Tumor Necrosis Factor-Alpha (TNF-a) Level
The normal result for TNF-a is <5.6 pg/mL.
Measured: Baseline, Post-Intervention (4 Weeks)
Change in 6 Minute Walk Test Score
Measured: Baseline, Post-Intervention (4 Weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startNov 2004
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Congenital DisordersStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William T. Mahle, MD, Emory University
- Investigators
- William T Mahle, MD, Principal investigator, Emory UniversityArshed Quyyumi, MD, Principal investigator, Emory UniversityWendy M Book, MD, Principal investigator, Emory UniversityMichael E McConnell, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00211081
- Sponsor's protocol ID
- 0954-2004
- Status last verified
- Oct 2017
- First submitted
- 13 Sep 2005
- Last updated
- 6 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 1359209Sorensen 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.
PubMed 7547018Celermajer 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.
PubMed 9247501Celermajer 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.
PubMed 8354824Anderson 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.
PubMed 10636260Gidding 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.
PubMed 3971523Yang SG, Rychik J. Mesenteric blood flow patterns: A link to protein-losing enteropathy after the Fontan operation. Circulation 1999;100-18:A3583.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Spironolactone on Endothelial Function in Patients With Single Ventricle Heart
- ClinicalTrials.gov ID
- NCT00211081
- Acronym / sponsor ID
- 0954-2004
- Conditions
- Congenital Disorders
- Keywords
- Congenital Heart Disease, Spironolactone, >17 years old, undergone Fontan procedure, endothelial function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Nov 2004
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Posted 16 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: Spironolactone (drug) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Single Ventricle Subjects
- >17 years
- have undergone Fontan Procedure
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Open Label |
Primary outcome
Change in Flow Mediated Dilation
Time frame: Baseline, Post-Intervention (4 Weeks)
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.
6 secondary outcomes
C-Reactive Protein Level
Time frame: Baseline, Post-Intervention (4 Weeks)
Interleukin-6 (IL-6) Level
Time frame: Baseline, Post-Intervention (4 Weeks)
Interleukin 1 Beta (IL1b) Level
Time frame: Baseline, Post-Intervention (4 Weeks)
Interleukin-10 (IL10) Level
Time frame: Baseline, Post-Intervention (4 Weeks)
Tumor Necrosis Factor-Alpha (TNF-a) Level
Time frame: Baseline, Post-Intervention (4 Weeks)
Change in 6 Minute Walk Test Score
Time frame: Baseline, Post-Intervention (4 Weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1359209Celermajer 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.
- Background: PubMed 7547018Sorensen 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.
- Background: PubMed 9247501Celermajer 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.
- Background: PubMed 8354824Celermajer 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.
- Background: PubMed 10636260Anderson 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.
- Background: PubMed 3971523Gidding 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.
- BackgroundYang SG, Rychik J. Mesenteric blood flow patterns: A link to protein-losing enteropathy after the Fontan operation. Circulation 1999;100-18:A3583.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William T Mahle, MD principal investigator
Emory University
Arshed Quyyumi, MD principal investigator
Emory University
Wendy M Book, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spironolactone (drug) in people with Congenital Disorders, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Flow Mediated Dilation (time frame: Baseline, Post-Intervention (4 Weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00211081, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2017.