Hypoplastic Left Heart SyndromeNCT02919956
Cerebral Anatomy, Hemodynamics and Metabolism
An observational study of Hypoplastic Left Heart Syndrome, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Single ventricle lesions are the leading cause of illness and death from congenital heart disease. The modified Fontan Operation is the corrective surgery for these lesions. The operation is done in stages over a few years and children who complete the operation are known to have greater neurodevelopmental (ND)… Read more about this study
- Who is it for?
- Ages 3 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypoplastic Left Heart Syndrome
- What is being tested?
- Magnetic Resonance Imaging and Neurodevelopmental Testing
- How many people
- 121 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 9 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
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 3 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Group I (cohort) will be patients enrolled in the original NIH CBF grant. Group II (cross-sectional) will be recruited from SV patients after Fontan operation but were not participants in the original study to enrich the patient population and to maximize Group I enrollment. Group III will be normal controls enrolled in the original CBF grant. Group IV will be patients at The Children's Hospital of Philadelphia (CHOP) for clinical MRIs and found to have structurally normal cardiac and brain anatomy. Parents/guardians of Group I-IV patients will be enrolled, as well. There will be a group of 1-5 volunteers enrolled to test the study MRI protocol. Volunteers will be patients who come to CHOP for clinical MRIs.
Who may be able to join
- SV Patients
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- SV Patients
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Cerebral Anatomy, Hemodynamics and Metabolism In Single Ventricles: Relationship to Neurodevelopment
Single ventricle lesions are the leading cause of illness and death from congenital heart disease. The modified Fontan Operation is the corrective surgery for these lesions. The operation is done in stages over a few years and children who complete the operation are known to have greater neurodevelopmental (ND) deficits than the general population. The purpose of this study is to understand how blood flow to the brain (CBF) and brain lesions relate to ND outcome, as well as how CMRO2 relates to anatomic brain lesions. These relationships will be studied through Magnetic Resonance Imaging (MRI) and ND Testing.
Read the detailed description
Single ventricle (SV) lesions are the leading cause of morbidity and mortality from congenital heart disease (CHD) in the United States. The definitive palliative surgery is the modified Fontan operation where systemic venous return is routed directly to the pulmonary arteries. The surgical reconstruction is performed in stages over a few years which includes the "Stage I" and hemiFontan or bidirectional Glenn operations. These children are known to have greater neurodevelopmental (ND) deficits than the general population and other forms of CHD. For example, a study at Children's Hospital of Philadelphia revealed that at 9 years old, 1/3 were receiving some form of special education; the median intelligence quotient (IQ) was 86 with mental retardation in 18%. One component to ultimate ND outcome is cerebral blood flow (CBF). Preliminary data in SV in the literature across all age ranges and multiple disease states, suggests that CBF is related to ND; a recent review of 25 studies bears this out. Another component to ND outcome is anatomic brain lesions. Preliminary data from a current NIH study of CBF study suggests a link between CBF and brain lesions (decreased CBF is associated with more brain lesions), weaving a complex interaction leading to ultimate ND outcome. There is a pressing need to understand CBF and brain lesions as it relates to childhood ND; this rapid growth stage may be especially important to ultimate cognitive function having not only a humanistic/social impact but a large economic one as well.
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
- Hypoplastic Left Heart Syndrome
- Being tested
- Magnetic Resonance Imaging, Neurodevelopmental Testing
- Keywords
- Single Ventricle, Fontan
- Medical subject headings
- Hypoplastic Left Heart Syndrome, Univentricular Heart
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingOther
Also called MRI
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 TestingOther
Also called ND 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Magnetic Resonance Imaging; Other: Neurodevelopmental Testing | |
| 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. Receives: Other: Magnetic Resonance Imaging; Other: Neurodevelopmental Testing | |
| 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. Receives: Other: Neurodevelopmental Testing | |
| 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. Receives: Other: Magnetic Resonance Imaging; Other: Neurodevelopmental Testing | |
| 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. Receives: Other: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relationship of CBF and Brain Abnormalities to ND Outcomes
This study proposes to recall SV patients from a cohort from a previous study to undergo an MRI (for anatomy, CBF and CMRO2) and ND testing. Normals from a previous grant will also be recalled to undergo ND testing. Correlations will be performed between ND, CBF and brain abnormalities from the a) original MRI, b) current study and c) change between the two. Response to hypercarbia will be assessed in a select group of patients. Additional SV patients and normals will be recruited to enrich the population. In addition, this study will determine how CBF and brain abnormalities in SV patients evolve over the course of time. Therefore, the timeframe for the comparisons will be a) from the original MRI to the current MRI and neurodevelopmental testing (up to 10 years) as well as b) the current MRI with neurodevelopmental testing.
Measured: Up to 10 years
Secondary outcomes (1)
Relationship of CMRO2 to ND outcome
This Aim will correlate CMRO2 as assessed in MRIs performed in the current study from Aim 1 to ND outcome. In addition, this proposal will relate CMRO2 to anatomic brain lesions by MRI. Therefore, the timeframe for the comparisons will be a) from the original MRI to the current MRI and neurodevelopmental testing (up to 10 years) as well as b) the current MRI with neurodevelopmental testing.
Measured: Up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study startApr 2016
- Primary completion9 Dec 2022
- Study completion9 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Hypoplastic Left Heart SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Mark A Fogel, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919956
- Sponsor's protocol ID
- 15-012291
- Other IDs
- 5R01HL090615-09
- Status last verified
- Dec 2024
- First submitted
- 2 Aug 2016
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Dr. Felix Werhil from the University of Penn will be analyzing the CMRO2 studies from the MRI images. Data will be transferred to him on a flash drive that has been encrypted and password-protected according to CHOP IT standards and hand delivered by the PI or a member of the study team. Dr. Alexandra Hanlon from University of Penn School of Nursing will be performing the statistics for the study. Investigators will have a REDCap database, which Dr. Hanlon has been approved for and received CHOP identity to access.
Publications
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.
PubMed 12084585Norwood 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.
PubMed 6153137Norwood 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.
PubMed 6847920Seliem 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.
PubMed 2527902Whitehead 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.
PubMed 19808629Glatz 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.
PubMed 22228054Dori 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.
PubMed 23322742Grosse-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.
PubMed 19808596Mahle 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.
PubMed 12354718Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971 May;26(3):240-8. doi: 10.1136/thx.26.3.240.
PubMed 5089489Fogel 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.
PubMed 37844519
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral Anatomy, Hemodynamics and Metabolism In Single Ventricles: Relationship to Neurodevelopment
- ClinicalTrials.gov ID
- NCT02919956
- Acronym / sponsor ID
- 15-012291
- Conditions
- Hypoplastic Left Heart Syndrome
- Keywords
- Single Ventricle, Fontan
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Apr 2016
- Primary completion
- 9 Dec 2022 (actual)
- Study completion
- 9 Dec 2022 (actual)
- First posted
- 30 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single ventricle lesions are the leading cause of illness and death from congenital heart disease. The modified Fontan Operation is the corrective surgery for these lesions. The operation is done in stages over a few years and children who complete the operation are known to have greater neurodevelopmental (ND) deficits than the general population. The purpose of this study is to understand how blood flow to the brain (CBF) and brain lesions relate to ND outcome, as well as how CMRO2 relates to anatomic brain lesions. These relationships will be studied through Magnetic Resonance Imaging (MRI) and ND Testing.
Detailed description
Single ventricle (SV) lesions are the leading cause of morbidity and mortality from congenital heart disease (CHD) in the United States. The definitive palliative surgery is the modified Fontan operation where systemic venous return is routed directly to the pulmonary arteries. The surgical reconstruction is performed in stages over a few years which includes the "Stage I" and hemiFontan or bidirectional Glenn operations. These children are known to have greater neurodevelopmental (ND) deficits than the general population and other forms of CHD. For example, a study at Children's Hospital of Philadelphia revealed that at 9 years old, 1/3 were receiving some form of special education; the median intelligence quotient (IQ) was 86 with mental retardation in 18%. One component to ultimate ND outcome is cerebral blood flow (CBF). Preliminary data in SV in the literature across all age ranges and multiple disease states, suggests that CBF is related to ND; a recent review of 25 studies bears this out. Another component to ND outcome is anatomic brain lesions. Preliminary data from a current NIH study of CBF study suggests a link between CBF and brain lesions (decreased CBF is associated with more brain lesions), weaving a complex interaction leading to ultimate ND outcome. There is a pressing need to understand CBF and brain lesions as it relates to childhood ND; this rapid growth stage may be especially important to ultimate cognitive function having not only a humanistic/social impact but a large economic one as well.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group I: CBF-I Single Ventricles | – | Other: Magnetic Resonance Imaging, Other: Neurodevelopmental TestingThe 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. |
| Group II: Prospective Single Ventricles | – | Other: Magnetic Resonance Imaging, Other: Neurodevelopmental TestingThe 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. |
| Group III: CBF-I Normal Controls | – | Other: Neurodevelopmental TestingThe 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. |
| Group IV: Prospective Normal Controls | – | Other: Magnetic Resonance Imaging, Other: Neurodevelopmental TestingThe 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. |
| Volunteer Group | – | Other: Magnetic Resonance ImagingThere 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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Group I (cohort) will be patients enrolled in the original NIH CBF grant. Group II (cross-sectional) will be recruited from SV patients after Fontan operation but were not participants in the original study to enrich the patient population and to maximize Group I enrollment. Group III will be normal controls enrolled in the original CBF grant. Group IV will be patients at The Children's Hospital of Philadelphia (CHOP) for clinical MRIs and found to have structurally normal cardiac and brain anatomy. Parents/guardians of Group I-IV patients will be enrolled, as well. There will be a group of 1-5 volunteers enrolled to test the study MRI protocol. Volunteers will be patients who come to CHOP for clinical MRIs.
Key inclusion criteria (14 listed)
- SV Patients
- 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
Key exclusion criteria (17 listed)
- SV Patients
- 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.
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 |
|---|---|---|
| Magnetic Resonance ImagingAlso: MRIAn 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. | Other | Group I: CBF-I Single Ventricles, Group II: Prospective Single Ventricles, Group IV: Prospective Normal Controls, Volunteer Group |
| Neurodevelopmental TestingAlso: ND TestingQuantitative 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 | Group I: CBF-I Single Ventricles, Group II: Prospective Single Ventricles, Group III: CBF-I Normal Controls, Group IV: Prospective Normal Controls |
Primary outcome
Relationship of CBF and Brain Abnormalities to ND Outcomes
Time frame: Up to 10 years
This study proposes to recall SV patients from a cohort from a previous study to undergo an MRI (for anatomy, CBF and CMRO2) and ND testing. Normals from a previous grant will also be recalled to undergo ND testing. Correlations will be performed between ND, CBF and brain abnormalities from the a) original MRI, b) current study and c) change between the two. Response to hypercarbia will be assessed in a select group of patients. Additional SV patients and normals will be recruited to enrich the population. In addition, this study will determine how CBF and brain abnormalities in SV patients evolve over the course of time. Therefore, the timeframe for the comparisons will be a) from the original MRI to the current MRI and neurodevelopmental testing (up to 10 years) as well as b) the current MRI with neurodevelopmental testing.
1 secondary outcome
Relationship of CMRO2 to ND outcome
Time frame: Up to 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Background: PubMed 12084585Hoffman 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.
- Background: PubMed 6153137Norwood 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.
- Background: PubMed 6847920Norwood 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.
- Background: PubMed 2527902Seliem 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.
- Background: PubMed 19808629Whitehead 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.
- Background: PubMed 22228054Glatz 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.
- Background: PubMed 23322742Dori 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.
- Background: PubMed 19808596Grosse-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.
- Background: PubMed 12354718Mahle 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.
- Background: PubMed 5089489Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971 May;26(3):240-8. doi: 10.1136/thx.26.3.240.
- Derived from this study: PubMed 37844519Fogel 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.
- Individual participant dataSharing planned: Yes. Dr. Felix Werhil from the University of Penn will be analyzing the CMRO2 studies from the MRI images. Data will be transferred to him on a flash drive that has been encrypted and password-protected according to CHOP IT standards and hand delivered by the PI or a member of the study team. Dr. Alexandra Hanlon from University of Penn School of Nursing will be performing the statistics for the study. Investigators will have a REDCap database, which Dr. Hanlon has been approved for and received CHOP identity to access.
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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.
Mark A Fogel, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypoplastic Left Heart Syndrome, run by Children's Hospital of Philadelphia 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 14 inclusion and 17 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 18 Dec 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Relationship of CBF and Brain Abnormalities to ND Outcomes (time frame: Up to 10 years). 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 NCT02919956, which also lists 11 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 18 Dec 2024.