Cerebral Anatomy, Hemodynamics and Metabolism

NCT02919956 | Completed DMC

• 2 other identifiers: 15-0122915R01HL090615-09
• Study Type: observational
• Target: 121
• Locations: 1 country
• Sites: 1

Brief 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) 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.

Conditions

Hypoplastic Left Heart Syndrome

Keywords

Single Ventricle; Fontan

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 10 years

Secondary Outcomes (1)

• Relationship of CMRO2 to ND outcome

  Up to 10 years

Study Arms (5)

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.

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.

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.

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.

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.

Other: Magnetic Resonance Imaging

Interventions

Magnetic Resonance Imaging OTHER

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.

Also known as: MRI

Group I: CBF-I Single Ventricles; Group II: Prospective Single Ventricles; Group IV: Prospective Normal Controls; Volunteer Group

Neurodevelopmental Testing OTHER

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.

Also known as: ND Testing

Group I: CBF-I Single Ventricles; Group II: Prospective Single Ventricles; Group III: CBF-I Normal Controls; Group IV: Prospective Normal Controls

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (11)

• 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.

  PMID: 12084585 BACKGROUND

• 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.

  PMID: 6153137 BACKGROUND

• 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.

  PMID: 6847920 BACKGROUND

• 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.

  PMID: 2527902 BACKGROUND

• 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.

  PMID: 19808629 BACKGROUND

• 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.

  PMID: 22228054 BACKGROUND

• 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.

  PMID: 23322742 BACKGROUND

• 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.

  PMID: 19808596 BACKGROUND

• 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.

  PMID: 12354718 BACKGROUND

• Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971 May;26(3):240-8. doi: 10.1136/thx.26.3.240.

  PMID: 5089489 BACKGROUND

• 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.

  PMID: 37844519 DERIVED

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Univentricular Heart

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Mark A Fogel, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: September 30, 2016
• Study Start: April 1, 2016
• Primary Completion: December 9, 2022
• Study Completion: December 9, 2022
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)