Congenital Heart DiseaseSVRIIINCT02692443
SVR III: Brain Connectome and Neurodevelopmental Outcomes
An observational study of Congenital Heart Disease, run by University of Pittsburgh.
Trial summary
Patients with hypoplastic left heart syndrome and other single right ventricle lesions who have undergone the Fontan procedure have a high risk of neurodevelopmental disorders that affect quality of life and adulthood employment. Read more about this study
- Who is it for?
- Ages 10 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Magnetic Resonance Imaging and Neurodevelopmental Testing
- Type of treatment
- Medical device, Lifestyle or therapy programme
- How many people
- 223 participants
- Where
- No sites listed yet
- Study dates
- Aug 2015to 30 Apr 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 10 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: SVR Survivor - male and female - 10 to 12 years of age
Who may be able to join
- SVR Survivor:
- All SVR study cohort members will be contacted to assess for vital status
- Transplant free survivors will be approached to participate in the in-person assessment
- Healthy Controls: Males and females aged 10 - 12 at the time of enrollment and whose parent or legal guardian can provide consent for participation will be recruited for participation in this study. Study participants will also be asked to provide assent for participation in this study.
Who cannot join
- SVR Survivors: The investigators will exclude patients who have undergone cardiac transplantation or biventricular conversion from all outcomes other than vital status.
- Those patients with a contraindication to MRI (i.e., claustrophobia; metal screen failure; inability to lie still) will not be enrolled for participation in this study.
- Healthy Controls: Potential participants will be excluded for any of the following reasons:
- disorders that would prevent successful completion of the planned study testing (e.g., pacemaker, metal implants; claustrophobia; inability to lie still)
- other forms of congenital heart disease requiring surgical correction
- Lack of reading fluency in English by primary caregiver in English
About this study
Official title: Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes
Patients with hypoplastic left heart syndrome and other single right ventricle lesions who have undergone the Fontan procedure have a high risk of neurodevelopmental disorders that affect quality of life and adulthood employment. This study will leverage the ongoing National Heart, Lung, and Blood Institute (NHLBI)-funded Single Ventricle Reconstruction Study by using innovative graph measures of brain connectivity to elucidate how alterations of the "connectome" in children with critical congenital heart disease are associated with developmental disabilities and their associated clinical risk factors. Improved understanding of these interrelationships may facilitate development of targeted interventions to improve outcome in the soaring population of adult Fontan survivors.
Read the detailed description
With dramatic improvement in survival of patients with hypoplastic left heart syndrome and related forms of single right ventricle undergoing staged palliation to the Fontan operation, a high prevalence of neurodevelopment abnormalities has been exposed. The NHLBI-funded Pediatric Heart Network (PHN) Single Ventricle Reconstruction (SVR) III study, "Long-term Outcomes of Children with Hypoplastic Left Heart Syndrome (HLHS) and the Impact of Norwood Shunt Type," is a prospective follow-up study of an existing cohort of children with HLHS and other single RV anomalies who were enrolled in early infancy in a randomized clinical trial of the modified Blalock-Taussig shunt (MBTS) versus right ventricular to pulmonary artery shunt (RVPAS). The parent SVR III study seeks to determine if the shunt assignment at the time of the Norwood operation is associated with cardiac function, transplant-free survival, exercise function, and neurodevelopmental outcomes. The investigators here propose a neuroimaging ancillary study to the parent SVRIII study that leverages the neurodevelopmental follow-up of the SVR cohort at age 11 years. The investigators will combine state-of-the-art brain imaging techniques [Resting-Blood Oxygenation Level Dependent (BOLD) and Diffusion Tensor Imaging] in 140 SVR III patients and 100 referent subjects with innovative brain connectome or "graph" analyses to determine if brain connectivity graph measurements will provide novel neuroimaging biomarkers for neurodevelopmental disabilities and improve the investigators' understanding of their inciting mechanisms in the SVR survivors. The investigators' specific aims are: Specific Aim (SA) #1: To characterize the global brain network topology of the SVR III cohort; SA #2: To determine which neurocognitive and behavioral outcomes predict global brain network topology in the SVR III cohort. SA #3: To determine which patient factors (e.g., birth weight, gestational age, maternal education) and medical factors (e.g., intraoperative conduct during Norwood procedure, hemodynamic complications, types and number of interventions, and measures of global morbidity) predict global brain network topology in the SVRIII cohort. SA #4: To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVRIII cohort. The investigators will use linear regression and mediation statistical methods to analyze associations of MRI graph measures with SVRIII neurodevelopmental measures and surgical/non-surgical clinical independent risk factors. Upon successful completion, these studies will elucidate the nature and basis of neurodevelopmental disability in single ventricle patients following Fontan palliation. This research will also contribute a novel and robust set of clinical/research tools in the form of neuroimaging biomarkers that can be used to help classify and predict outcomes in complex congenital heart disease (CHD).
- Conditions
- Congenital Heart Disease
- Being tested
- Magnetic Resonance Imaging, Neurodevelopmental Testing
- Keywords
- Congenital Heart Disease, Magnetic Brain Resonance, CHD, MRI, Neurodevelopmental
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingDevice
Brain MRI without Contrast
Neurodevelopmental TestingBehavioural
Validated battery of neurodevelopmental and psychological tests.
| Study group | Role | What they receive |
|---|---|---|
| SVR Survivors | Through the SVR and SVR II studies vital status has been followed annually for the entire SVR cohort. As of June 2014 352 subjects are alive, 18 of whom have undergone cardiac transplantation, and 18 have undergone biventricular conversion leaving 334 transplant-free survivors with single ventricle physiology. Each patient enrolled to this ancillary study from the parent SVR study will be asked to undergo Magnetic Resonance Imaging (Brain MRI without Contrast) in addition to the already scheduled parent study follow-up procedures. Receives: Device: Magnetic Resonance Imaging; Behavioral: Neurodevelopmental Testing | |
| Healthy Controls | In addition to the SVR survivors, investigators plan to enroll 100 age- and gender-matched healthy controls. Healthy controls enrolled for participation in this ancillary study will be asked to undergo Magnetic Resonance Imaging (Brain MRI without Contrast) in addition to completing the Neurodevelopmental Testing Battery that is already part of the parent SVR study and completed by SVR Survivors as part of their SVR follow-up appointments. Receives: Device: Magnetic Resonance Imaging; Behavioral: Neurodevelopmental Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI and neurodevelopmental outcomes in CHD patients as compared to their healthy counterparts
To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVRIII cohort.
Measured: Through study completion, an average of 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2016 (estimated)
- Study startAug 2015
- Primary completion30 Apr 2022
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Prospective
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital of Philadelphia, Emory University, Medical College of Wisconsin, University of Michigan
- Responsible party
- Principal investigator, Ashok Panigrahy, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02692443
- Sponsor's protocol ID
- R01HL128818
- Acronym
- SVRIII
- Status last verified
- May 2022
- First submitted
- 24 Sep 2015
- Last updated
- 9 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be supplied in the required, standard de-identified format and made available without cost to researchers or analysts. Access to databases and associated software tools generated under the project will be available for educational, research and non-profit purposes.
Publications
Schmithorst V, Ceschin R, Lee V, Wallace J, Sahel A, Chenevert T, Parmar H, Berman JI, Vossough A, Qiu D, Kadom N, Grant PE, Gagoski B, LaViolette P, Maheshwari M, Sleeper LA, Bellinger D, Ilardi D, O'Neil S, Miller TA, Detterich J, Hill KD, Atz AM, Richmond M, Cnota J, Mahle WT, Ghanayem N, Gaynor W, Goldberg CS, Newburger JW, Panigrahy A. Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study. medRxiv [Preprint]. 2023 Apr 17:2023.04.12.23288433. doi: 10.1101/2023.04.12.23288433.
PubMed 37131744
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes
- ClinicalTrials.gov ID
- NCT02692443
- Acronym / sponsor ID
- SVRIII / R01HL128818
- Conditions
- Congenital Heart Disease
- Keywords
- Congenital Heart Disease, Magnetic Brain Resonance, CHD, MRI, Neurodevelopmental
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital of Philadelphia, Emory University, Medical College of Wisconsin, University of Michigan
- Study start
- Aug 2015
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 26 Feb 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.
Patients with hypoplastic left heart syndrome and other single right ventricle lesions who have undergone the Fontan procedure have a high risk of neurodevelopmental disorders that affect quality of life and adulthood employment. This study will leverage the ongoing National Heart, Lung, and Blood Institute (NHLBI)-funded Single Ventricle Reconstruction Study by using innovative graph measures of brain connectivity to elucidate how alterations of the "connectome" in children with critical congenital heart disease are associated with developmental disabilities and their associated clinical risk factors. Improved understanding of these interrelationships may facilitate development of targeted interventions to improve outcome in the soaring population of adult Fontan survivors.
Detailed description
With dramatic improvement in survival of patients with hypoplastic left heart syndrome and related forms of single right ventricle undergoing staged palliation to the Fontan operation, a high prevalence of neurodevelopment abnormalities has been exposed. The NHLBI-funded Pediatric Heart Network (PHN) Single Ventricle Reconstruction (SVR) III study, "Long-term Outcomes of Children with Hypoplastic Left Heart Syndrome (HLHS) and the Impact of Norwood Shunt Type," is a prospective follow-up study of an existing cohort of children with HLHS and other single RV anomalies who were enrolled in early infancy in a randomized clinical trial of the modified Blalock-Taussig shunt (MBTS) versus right ventricular to pulmonary artery shunt (RVPAS). The parent SVR III study seeks to determine if the shunt assignment at the time of the Norwood operation is associated with cardiac function, transplant-free survival, exercise function, and neurodevelopmental outcomes. The investigators here propose a neuroimaging ancillary study to the parent SVRIII study that leverages the neurodevelopmental follow-up of the SVR cohort at age 11 years. The investigators will combine state-of-the-art brain imaging techniques [Resting-Blood Oxygenation Level Dependent (BOLD) and Diffusion Tensor Imaging] in 140 SVR III patients and 100 referent subjects with innovative brain connectome or "graph" analyses to determine if brain connectivity graph measurements will provide novel neuroimaging biomarkers for neurodevelopmental disabilities and improve the investigators' understanding of their inciting mechanisms in the SVR survivors. The investigators' specific aims are: Specific Aim (SA) #1: To characterize the global brain network topology of the SVR III cohort; SA #2: To determine which neurocognitive and behavioral outcomes predict global brain network topology in the SVR III cohort. SA #3: To determine which patient factors (e.g., birth weight, gestational age, maternal education) and medical factors (e.g., intraoperative conduct during Norwood procedure, hemodynamic complications, types and number of interventions, and measures of global morbidity) predict global brain network topology in the SVRIII cohort. SA #4: To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVRIII cohort. The investigators will use linear regression and mediation statistical methods to analyze associations of MRI graph measures with SVRIII neurodevelopmental measures and surgical/non-surgical clinical independent risk factors. Upon successful completion, these studies will elucidate the nature and basis of neurodevelopmental disability in single ventricle patients following Fontan palliation. This research will also contribute a novel and robust set of clinical/research tools in the form of neuroimaging biomarkers that can be used to help classify and predict outcomes in complex congenital heart disease (CHD).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SVR Survivors | – | Device: Magnetic Resonance Imaging, Behavioral: Neurodevelopmental TestingThrough the SVR and SVR II studies vital status has been followed annually for the entire SVR cohort. As of June 2014 352 subjects are alive, 18 of whom have undergone cardiac transplantation, and 18 have undergone biventricular conversion leaving 334 transplant-free survivors with single ventricle physiology. Each patient enrolled to this ancillary study from the parent SVR study will be asked to undergo Magnetic Resonance Imaging (Brain MRI without Contrast) in addition to the already scheduled parent study follow-up procedures. |
| Healthy Controls | – | Device: Magnetic Resonance Imaging, Behavioral: Neurodevelopmental TestingIn addition to the SVR survivors, investigators plan to enroll 100 age- and gender-matched healthy controls. Healthy controls enrolled for participation in this ancillary study will be asked to undergo Magnetic Resonance Imaging (Brain MRI without Contrast) in addition to completing the Neurodevelopmental Testing Battery that is already part of the parent SVR study and completed by SVR Survivors as part of their SVR follow-up appointments. |
Who may qualify
- Ages
- 10 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- SVR Survivor - male and female - 10 to 12 years of age
Key inclusion criteria (4 listed)
- SVR Survivor:
- All SVR study cohort members will be contacted to assess for vital status
- Transplant free survivors will be approached to participate in the in-person assessment
- Healthy Controls: Males and females aged 10 - 12 at the time of enrollment and whose parent or legal guardian can provide consent for participation will be recruited for participation in this study. Study participants will also be asked to provide assent for participation in this study.
Key exclusion criteria (6 listed)
- SVR Survivors: The investigators will exclude patients who have undergone cardiac transplantation or biventricular conversion from all outcomes other than vital status.
- Those patients with a contraindication to MRI (i.e., claustrophobia; metal screen failure; inability to lie still) will not be enrolled for participation in this study.
- Healthy Controls: Potential participants will be excluded for any of the following reasons:
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 ImagingBrain MRI without Contrast | Device | Healthy Controls, SVR Survivors |
| Neurodevelopmental TestingValidated battery of neurodevelopmental and psychological tests. | Behavioural | Healthy Controls, SVR Survivors |
Primary outcome
MRI and neurodevelopmental outcomes in CHD patients as compared to their healthy counterparts
Time frame: Through study completion, an average of 4 years
To precisely characterize the specific relationships between global brain network topology, specific patient/medical factors, and adverse neurocognitive/behavioral outcomes in the SVRIII cohort.
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 9 May 2022.
- Derived from this study: PubMed 37131744Schmithorst V, Ceschin R, Lee V, Wallace J, Sahel A, Chenevert T, Parmar H, Berman JI, Vossough A, Qiu D, Kadom N, Grant PE, Gagoski B, LaViolette P, Maheshwari M, Sleeper LA, Bellinger D, Ilardi D, O'Neil S, Miller TA, Detterich J, Hill KD, Atz AM, Richmond M, Cnota J, Mahle WT, Ghanayem N, Gaynor W, Goldberg CS, Newburger JW, Panigrahy A. Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study. medRxiv [Preprint]. 2023 Apr 17:2023.04.12.23288433. doi: 10.1101/2023.04.12.23288433.
- Individual participant dataSharing planned: Yes. Data will be supplied in the required, standard de-identified format and made available without cost to researchers or analysts. Access to databases and associated software tools generated under the project will be available for educational, research and non-profit purposes.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease, run by University of Pittsburgh.
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 4 inclusion and 6 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 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
MRI and neurodevelopmental outcomes in CHD patients as compared to their healthy counterparts (time frame: Through study completion, an average of 4 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 NCT02692443, which also lists 1 linked publication.
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 9 May 2022.