Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
121 participants
OBSERVATIONAL
2016-04-30
2022-12-09
Brief Summary
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Detailed Description
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Data from a previous NIH grant which ended November 2014 indicates that CBF in SV patients changes throughout the staged surgeries and in the first 2 stages, under stressed conditions such as hypercarbia; in addition, initial look at the data suggests a difference in brain abnormalities as well. These children are especially at risk for altered CBF and brain abnormalities with their changing physiology. At Stage I, a "runoff" physiology is present created by the aorto-pulmonary shunt potentially causing a "steal" from the cerebral circulation. In the 2nd stage (e.g. hemiFontan), cerebral and pulmonary circulations are connected directly and exclusively in series with each other; aortic blood flows to the brain and then directly to the lungs via the superior vena cava. After Fontan completion, downstream cerebral venous pressures are elevated. Finally, SV patients develop aorto-pulmonary collaterals (APC) at all stages and another ongoing research project found a strong inverse correlation between CBF and the degree of APC flow, further putting CBF of SV at risk.
In another study, magnetic resonance imaging (MRI) was utilized to measure blood flow and visualize cerebral anatomy by phase contrast MRI arterial spin labeling and anatomic imaging such as T1 weighted sequences and diffusion tensor imaging. MRI utilizing susceptometry (oximetry) recently developed by an investigator on this renewal, can also quantify the cerebral metabolic rate of oxygen consumption (CMRO2). This combination of MRI capabilities offers a unique opportunity to assess cerebral anatomy, hemodynamics and oxygen metabolism in the same study; by combining this with ND testing, this study is poised to link the two in the hopes of not only understanding cognitive function but to positively intervene in ND outcome. A comprehensive assessment of brain anatomy and function linked to ND outcomes has never been reported in any group of patients nor with utilizing measures at 2 time points.
This is a prospective, single center study of SV patients and seeks to relate cerebral anatomy, hemodynamics and CMRO2 with ND outcome using another patient cohort obtained under a previous study as a basis and utilizing data from 2 time points (original grant and renewal). This approach along with using cerebral carbon dioxide (CO2) reactivity and CMRO2 are major strengths of this study. Elucidating these factors may ultimately lead to modifications in management (e.g. timing of surgery) and identifying children at cognitive risk to implement early intervention and possibly improve ND outcome.
Conditions
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Keywords
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Study Design
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COHORT
CROSS_SECTIONAL
Study Groups
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Group I: CBF-I Single Ventricles
The 1st group (cohort group) will be patients who were enrolled in the original NIH CBF grant. These patients will undergo a 60-90 minute Magnetic Resonance Imaging scan of the brain and heart. They will also have Neurodevelopmental Testing.
Magnetic Resonance Imaging
An MRI scan takes pictures of the brain and heart using a magnet and radio waves. During scanning, measurements of oxygen delivery to the brain will be obtained (CMRO2) as well as evaluation of the heart as it relates to the brain. During the scan patients will be monitored for safety by ECG, blood pressure, television camera, pulse oximetry, and carbon dioxide measurements. Cardiac anesthesiologist and cardiologist will be present.
Neurodevelopmental Testing
Quantitative ND tests and standardized rating scales will be used in the areas of intellectual, adaptive, visual motor skills, academic achievement in math and reading, attention and executive functioning , motor skills, memory, language, social skills and behavior. Neurodevelopmental Testing will last approximately 3.5-4 hours. Testing will be done through the Neurobehavioral Core at CHOP. Breaks will be taken as needed and a one hour lunch break will be taken, if applicable. ND testing will be performed prior to MRI (if on the same day) or on a different day than the MRI to promote engagement and best performance.
Group II: Prospective Single Ventricles
The 2nd group (cross sectional group) will be prospectively recruited from SV patients after Fontan operation but were not participants in the original study and will be age matched to Group I to enrich the patient population. These patients will undergo a 60-90 minute Magnetic Resonance Imaging scan of the brain and heart. They will also have Neurodevelopmental Testing.
Magnetic Resonance Imaging
An MRI scan takes pictures of the brain and heart using a magnet and radio waves. During scanning, measurements of oxygen delivery to the brain will be obtained (CMRO2) as well as evaluation of the heart as it relates to the brain. During the scan patients will be monitored for safety by ECG, blood pressure, television camera, pulse oximetry, and carbon dioxide measurements. Cardiac anesthesiologist and cardiologist will be present.
Neurodevelopmental Testing
Quantitative ND tests and standardized rating scales will be used in the areas of intellectual, adaptive, visual motor skills, academic achievement in math and reading, attention and executive functioning , motor skills, memory, language, social skills and behavior. Neurodevelopmental Testing will last approximately 3.5-4 hours. Testing will be done through the Neurobehavioral Core at CHOP. Breaks will be taken as needed and a one hour lunch break will be taken, if applicable. ND testing will be performed prior to MRI (if on the same day) or on a different day than the MRI to promote engagement and best performance.
Group III: CBF-I Normal Controls
The 3rd group (cohort group) will be normal controls who were enrolled in the original CBF grant. These patients will have Neurodevelopmental Testing. The data from these patients' MRI from CBF-I (original CBF grant) will be used.
Neurodevelopmental Testing
Quantitative ND tests and standardized rating scales will be used in the areas of intellectual, adaptive, visual motor skills, academic achievement in math and reading, attention and executive functioning , motor skills, memory, language, social skills and behavior. Neurodevelopmental Testing will last approximately 3.5-4 hours. Testing will be done through the Neurobehavioral Core at CHOP. Breaks will be taken as needed and a one hour lunch break will be taken, if applicable. ND testing will be performed prior to MRI (if on the same day) or on a different day than the MRI to promote engagement and best performance.
Group IV: Prospective Normal Controls
The 4th group (cross sectional group) will be prospectively recruited from patients who come to Children's Hospital of Philadelphia (CHOP) for clinically indicated MRIs and found to have structurally normal cardiac and brain anatomy. These patients will have an abbreviated research MRI, lasting 15-20 minutes, added onto their clinically-indicated MRI at CHOP. They will also have Neurodevelopmental Testing.
Magnetic Resonance Imaging
An MRI scan takes pictures of the brain and heart using a magnet and radio waves. During scanning, measurements of oxygen delivery to the brain will be obtained (CMRO2) as well as evaluation of the heart as it relates to the brain. During the scan patients will be monitored for safety by ECG, blood pressure, television camera, pulse oximetry, and carbon dioxide measurements. Cardiac anesthesiologist and cardiologist will be present.
Neurodevelopmental Testing
Quantitative ND tests and standardized rating scales will be used in the areas of intellectual, adaptive, visual motor skills, academic achievement in math and reading, attention and executive functioning , motor skills, memory, language, social skills and behavior. Neurodevelopmental Testing will last approximately 3.5-4 hours. Testing will be done through the Neurobehavioral Core at CHOP. Breaks will be taken as needed and a one hour lunch break will be taken, if applicable. ND testing will be performed prior to MRI (if on the same day) or on a different day than the MRI to promote engagement and best performance.
Volunteer Group
There will also be a volunteer group of one to five volunteers that will be enrolled prior to enrollment in the other four study groups. These volunteers will be prospectively recruited from patients who come to Children's Hospital of Philadelphia (CHOP) for a clinically-indicated MRI and consent to have an additional 15-20 minutes of research MRI scanning. The purpose will be to ensure that the brain MRI sequences run correctly and produce useful information before the patient and normal control enrollment begins. The volunteers will not undergo neurodevelopmental testing.
Magnetic Resonance Imaging
An MRI scan takes pictures of the brain and heart using a magnet and radio waves. During scanning, measurements of oxygen delivery to the brain will be obtained (CMRO2) as well as evaluation of the heart as it relates to the brain. During the scan patients will be monitored for safety by ECG, blood pressure, television camera, pulse oximetry, and carbon dioxide measurements. Cardiac anesthesiologist and cardiologist will be present.
Interventions
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Magnetic Resonance Imaging
An MRI scan takes pictures of the brain and heart using a magnet and radio waves. During scanning, measurements of oxygen delivery to the brain will be obtained (CMRO2) as well as evaluation of the heart as it relates to the brain. During the scan patients will be monitored for safety by ECG, blood pressure, television camera, pulse oximetry, and carbon dioxide measurements. Cardiac anesthesiologist and cardiologist will be present.
Neurodevelopmental Testing
Quantitative ND tests and standardized rating scales will be used in the areas of intellectual, adaptive, visual motor skills, academic achievement in math and reading, attention and executive functioning , motor skills, memory, language, social skills and behavior. Neurodevelopmental Testing will last approximately 3.5-4 hours. Testing will be done through the Neurobehavioral Core at CHOP. Breaks will be taken as needed and a one hour lunch break will be taken, if applicable. ND testing will be performed prior to MRI (if on the same day) or on a different day than the MRI to promote engagement and best performance.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Subjects ages 3 to 15 years old who have completed their Fontan procedure and their parents/guardians.
* Any complex congenital heart lesion that has SV physiology of either right ventricle (RV) or left ventricle (LV) morphology.
* Ability to undergo a 60-90 minute MRI scan under general anesthesia or deep sedation if general anesthesia or sedation is needed.
* Parents signing informed consent. Healthy Controls
* Males and females ages 3 to 15 years old if in the original cohort and if not in the original cohort, age matched with Groups I and II, and their parents/guardians.
* Normal cerebral and cardiac anatomy who are normocephalic and who are asymptomatic.
* For normal controls being prospectively enrolled and not part of the original grant, the ability to extend the clinical MRI an extra 15-20 minutes.
* For normal controls undergoing sedation, the ability to extend anesthesia for approximately 15-30 minutes for research purposes only.
* Parents signing informed consent. Volunteers
* Patients who come to CHOP for a clinically indicated MRI.
* The ability to extend the clinical MRI an extra 15-20 minutes.
* If 18 or over, patient signing informed consent.
* If under 18, parents signing informed consent.
Exclusion Criteria
* A patient whose primary language is not English. Patients who speak English who have parents or guardians who do not speak English would not be excluded.
* Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
* Any known significant neurological disease outside of the usual state of SV patients.
* Any major anomalies which would confound neurological outcome.
* A patient with a pacemaker or cardioverter/defibrillator in place.
* A contraindicated ferromagnetic foreign body).
* Pregnancy Healthy Controls
* An individual whose primary language is not English. Patients who speak English who have parents or guardians who do not speak English would not be excluded
* Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
* Any known significant neurological disease.
* Any contraindication to extending the MRI.
* Pregnancy. Volunteers
* A patient whose primary language is not English. Patients who speak English who have parents or guardians who do not speak English would not be excluded.
* Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
* Any contraindication to extending the MRI.
* Pregnancy.
3 Years
ALL
Yes
Sponsors
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Children's Hospital of Philadelphia
OTHER
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Responsible Party
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Principal Investigators
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Mark A Fogel, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital of Philadelphia
Locations
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Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Countries
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References
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Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900. doi: 10.1016/s0735-1097(02)01886-7.
Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart syndrome: experience with palliative surgery. Am J Cardiol. 1980 Jan;45(1):87-91. doi: 10.1016/0002-9149(80)90224-6.
Norwood WI, Lang P, Hansen DD. Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med. 1983 Jan 6;308(1):23-6. doi: 10.1056/NEJM198301063080106. No abstract available.
Seliem M, Muster AJ, Paul MH, Benson DW Jr. Relation between preoperative left ventricular muscle mass and outcome of the Fontan procedure in patients with tricuspid atresia. J Am Coll Cardiol. 1989 Sep;14(3):750-5. doi: 10.1016/0735-1097(89)90121-6.
Whitehead KK, Gillespie MJ, Harris MA, Fogel MA, Rome JJ. Noninvasive quantification of systemic-to-pulmonary collateral flow: a major source of inefficiency in patients with superior cavopulmonary connections. Circ Cardiovasc Imaging. 2009 Sep;2(5):405-11. doi: 10.1161/CIRCIMAGING.108.832113. Epub 2009 Jul 8.
Glatz AC, Rome JJ, Small AJ, Gillespie MJ, Dori Y, Harris MA, Keller MS, Fogel MA, Whitehead KK. Systemic-to-pulmonary collateral flow, as measured by cardiac magnetic resonance imaging, is associated with acute post-Fontan clinical outcomes. Circ Cardiovasc Imaging. 2012 Mar;5(2):218-25. doi: 10.1161/CIRCIMAGING.111.966986. Epub 2012 Jan 6.
Dori Y, Glatz AC, Hanna BD, Gillespie MJ, Harris MA, Keller MS, Fogel MA, Rome JJ, Whitehead KK. Acute effects of embolizing systemic-to-pulmonary arterial collaterals on blood flow in patients with superior cavopulmonary connections: a pilot study. Circ Cardiovasc Interv. 2013 Feb;6(1):101-6. doi: 10.1161/CIRCINTERVENTIONS.112.972265. Epub 2013 Jan 15.
Grosse-Wortmann L, Al-Otay A, Yoo SJ. Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion: quantification with MRI. Circ Cardiovasc Imaging. 2009 May;2(3):219-25. doi: 10.1161/CIRCIMAGING.108.834192. Epub 2009 Mar 25.
Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002 Sep 24;106(12 Suppl 1):I109-14.
Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971 May;26(3):240-8. doi: 10.1136/thx.26.3.240.
Fogel MA, Donnelly E, Crandell I, Hanlon A, Whitehead KK, Harris M, Partington S, Biko D, Flynn T, Nicolson S, Gaynor JW, Licht D, Vossough A. Cerebral Blood Flow, Brain Injury, and Aortic-Pulmonary Collateral Flow After the Fontan Operation. Am J Cardiol. 2023 Dec 1;208:164-170. doi: 10.1016/j.amjcard.2023.08.023. Epub 2023 Oct 14.
Other Identifiers
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15-012291
Identifier Type: -
Identifier Source: org_study_id