SVR III: Brain Connectome and Neurodevelopmental Outcomes (SVRIII)

May 5, 2022 updated by: Ashok Panigrahy, University of Pittsburgh

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
223

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

10 years to 12 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

SVR Survivor - male and female - 10 to 12 years of age

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. disorders that would prevent successful completion of the planned study testing (e.g., pacemaker, metal implants; claustrophobia; inability to lie still)
    2. other forms of congenital heart disease requiring surgical correction
    3. Lack of reading fluency in English by primary caregiver in English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Device: Magnetic Resonance Imaging
Brain MRI without Contrast
Behavioral: Neurodevelopmental Testing
Validated battery of neurodevelopmental and psychological tests.
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.
Device: Magnetic Resonance Imaging
Brain MRI without Contrast
Behavioral: Neurodevelopmental Testing
Validated battery of neurodevelopmental and psychological tests.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Through study completion, an average of 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pittsburgh

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Children's Hospital of Philadelphia
University of Michigan
Boston Children's Hospital
Emory University
Medical College of Wisconsin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 24, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R01HL128818 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

After all study subjects have completed participation and analysis have been completed.

IPD Sharing Access Criteria

Data will be shared through secure website with interested research and accessible only by username and password provided by PI research team.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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