Clinical trial NCT02135081: Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction
Official title: A Magnetic Resonance Imaging Study to Determine Cerebral Blood Flow Changes in Single Ventricle Patients During Staged Reconstruction as Compared to Normal Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Single Ventricle Defect
Keywords: Single ventricle
Hypoplastic Left Heart Syndrome
Congenital heart lesion
Right or left ventricle
Cerebral blood flow
Pulmonary blood flow
Staged Fontan reconstruction
hemi Fontan/bidirectional Glenn stages
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2014-05-09
Enrollment: 260
Sex: ALL
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Single ventricle patients will be recruited from the cohort of patients treated and/or followed at The Children's Hospital of Philadelphia in the cardiology program and surrounding hospitals/institutions. In specific, patients will be approached to participate in the study during clinic visits or visits to the hospital for other reasons. Children for the normal control group will be recruited from children who are undergoing clinical MRIs at CHOP. A full understanding of all study related procedures and processes will be explained to the subject, including all MRI scans, how the MRI scanner works and how the proposed research will help medical practice. Children likely to have a normal brain MRI will be asked to participate and sign an informed consent form.

Brief summary: This study seeks to determine cerebral blood flow changes in single ventricle patients during staged surgical reconstruction as compared with normal children. Two general groups of single ventricle patients will be recruited for this study, corresponding to the two approaches used. An aged-match group of healthy subjects will be included as a control.

Detailed description: This is a prospective, non-randomized, single center study designed to measure and determine the changes in cerebral blood flow in a cohort of single ventricle patients followed across all three stages of surgical (Fontan) reconstruction. In addition, cerebral blood flow response to hypercarbia will be determined after the first 2 operations as a measure of cerebral blood flow reserve and the "intactness" of the cerebral autoregulatory system. MRI data from this cohort will be compared with that collected in age-matched healthy children and in a cross sectional group of patients who will not necessarily be followed through all stages of surgery, but may undergo one or two of the MRI evaluations depending on their stage of surgery. Neurological exams and EEGs will be performed. Medical history, cardiac catheterization data, where available, will also be collected. Factors such as cardiopulmonary bypass time and socioeconomic class will be controlled for.

Eligibility criteria: Inclusion Criteria - Single Ventricle Subjects:

* Males or females up to age 10 years.
* Any complex congenital heart lesion that has single ventricle physiology. These single ventricle lesions will be of either right or left ventricular morphology.
* Ability to undergo an MRI scan of at least 60-90 minutes under general anesthesia or deep sedation. Patients will undergo determination of their physical ability to undergo the MRI prior to being enrolled in the study by parameters such as blood pressure, heart rate, cardiac rhythm, and respiratory rate. MRI involves laying still in the supine position for at least 60-90 minutes.
* Parents signing informed consent.

Inclusion Criteria - Normal Control Group:

* Males or females up to age 10 years.
* Normal cerebral anatomy who are normocephalic and who are asymptomatic (e.g. if the scan is performed for headache) at the time of the scan.
* Ability to undergo an MRI scan of at least 60-90 minutes under general anesthesia or deep sedation. Normal patients will undergo determination of their physical ability to undergo the MRI prior to being enrolled in the study by parameters such as blood pressure, heart rate, cardiac rhythm, and respiratory rate. MRI involves laying still in the supine position for at least 60-90 minutes.
* Parents signing informed consent.

Exclusion Criteria - Single Ventricle Patients :

* Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
* Stenosis of the branch pulmonary arteries or coarctation of the aorta.
* Any significant arrhythmias such as supraventricular tachycardia, trigeminy, etc. Occasional premature atrial or ventricular contractions or an occasional missed beat is permitted.
* Systemic hypertension.
* Primary lung disease (eg bronchopulmonary dysplasia).
* Any known significant neurological disease outside of the usual state of single ventricle patients.
* Any chromosomal anomalies or other major anomalies which would confound neurological outcome.
* A patient with a pacemaker or cardioverter/defibrillator in place.
* A ferromagnetic foreign body (with the exception of sternal wires and vascular clips in the thorax).
* Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Exclusion Criteria - Normal Control Group:

* 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 performing an MRI.
* Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Primary outcomes:
measure: Cerebral blood flow changes throughout staged surgical reconstruction in single ventricle patients.
timeFrame: Up to 2 years
Secondary outcomes:
measure: CBF in single ventricle patients compared to CBF of age-matched normal children.
timeFrame: Up to 2 years
measure: CBF reserve and "intactness" of the cerebral regulatory mechanisms after Stage I and hemi Fontan/bidirectional Glenn stage of surgeries.
timeFrame: Up to 2 years
measure: CBF reserve after Stage 1 compared with CBF reserve in hemi Fontan/bidirectional Glenn stage of surgeries.
timeFrame: Up to 2 years
Other outcomes:
measure: Age related CBF changes between 4-6 months to 3-10 years.
timeFrame: Up to 2 hours
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: CHOP Physician
name: Mark Fogel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fogel MA, Li C, Elci OU, Pawlowski T, Schwab PJ, Wilson F, Nicolson SC, Montenegro LM, Diaz L, Spray TL, Gaynor JW, Fuller S, Mascio C, Keller MS, Harris MA, Whitehead KK, Bethel J, Vossough A, Licht DJ. Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction. Circulation. 2017 Feb 14;135(7):671-682. doi: 10.1161/CIRCULATIONAHA.116.021724. Epub 2016 Dec 28.
citation: Fogel MA, Li C, Wilson F, Pawlowski T, Nicolson SC, Montenegro LM, Diaz Berenstein L, Spray TL, Gaynor JW, Fuller S, Keller MS, Harris MA, Whitehead KK, Clancy R, Elci O, Bethel J, Vossough A, Licht DJ. Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles. Heart. 2015 Aug;101(16):1325-31. doi: 10.1136/heartjnl-2014-307311. Epub 2015 Jun 5.