MINDS Imaging Ancillary Study

Adult Congenital Heart Disease Clinical Trial

— MINDS  

Official title:

MINDS Imaging Ancillary Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05270356
• Other study ID #: STUDY21020073
• Secondary ID: R01HL152740
• Status: Enrolling by invitation
• Start date: May 27, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: January 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is an ancillary study to the NHLBI-funded Pediatric Heart Network (PHN) "Multi-Institutional Neurocognitive Discovery Study" (MINDS) in Adult Congenital Heart Disease (ACHD). The MINDS-ACHD" study will recruit 500 complex CHD patients between18-30 years old. The investigators propose to quantitate multi-modal neuroimaging biomarkers (brain injury, structure and physiology) which are not only important components of brain and cognitive reserve but can be predictive of neurocognitive decline and early onset of dementia in the aging non-CHD population.

Description:

Dramatic advances in management of congenital heart disease (CHD) have improved survival to adulthood from <10% in the 1960's to nearly 90% in the current era. With this shifting demographic, adult CHD (ACHD) patients now outnumber pediatric CHD patients. ACHD patients demonstrate domain-specific neurocognitive deficits such as impairment in executive function, associated with reduced quality of life that includes deficits in educational attainment and social interaction. These deficits are related to risk factors that can occur across the lifespan, including genetic abnormalities, cumulative hypoxic/ischemic injury, and, adult-onset atherosclerotic cerebrovascular disease. The overarching hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits, including executive dysfunction, which are modified by behavioral and environmental enrichment proxies of CR (e.g., level of education and lifestyle/social habits). The investigators propose an ancillary study to the NHLBI-funded Pediatric Heart Network (PHN) "Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)." The investigators will leverage the MINDS-ACHD parent study data (i.e., NIH Toolbox neuropsychological battery/clinical data/biological samples) and an established neuroimaging harmonization, which the investigators currently use for the PHN Single Ventricle Reconstruction (SVRIII) multi-center brain connectome study (R01-HL128818), to measure neuroimaging biomarkers in ACHD patients at the same PHN sites. The specific aims are: Specific Aim #1 (brain injury): To determine if vascular-related brain injury (cortical infarcts, hemosiderin lesions, and white matter hyperintensity) is associated with specific neurocognitive deficits (e.g. NIH Toolbox total composite score) in ACHD patients. Specific Aim #2 (brain structure): To determine if reduced fronto-temporal cortical thickness and white matter connectivity are associated with specific neurocognitive deficits (e.g. NIH Toolbox frontal executive sub-score) in ACHD patients. Specific Aim #3 (brain physiology): To determine if reduced cerebrovascular reserve (regional cerebral blood flow/ resting BOLD imaging) is associated with specific neurocognitive deficits (e.g. NIH Toolbox crystallized composite score) in ACHD patients. Specific Aim #4 (cognitive reserve): To determine if the associations between neuroimaging biomarkers and neurocognitive outcomes in ACHD patients are modified by behavioral and environmental enrichment proxies of CR, using traditional statistical models and machine learning techniques. Given the paucity of multi-modal neuroimaging studies in ACHD, the proposed study addresses a major knowledge gap in the ACHD population by providing insight into the mechanism underlying impaired neurocognitive outcomes. This study will provide structural-physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging study to be performed in ACHD. Importantly, other behavioral and environmental enrichment data will be integrated with these neuroimaging and neurocognitive outcome data to model cognitive reserve. Results from this research will help shape the care of ACHD patients, and further our understanding of the interplay between brain injury and cognitive reserve. The proposed ancillary study is thus both feasible and cost-effective by leveraging the NHLBI-PHN infrastructure. As such, the proposed research is well aligned with the NHLBI's Strategic Vision.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 156
• Est. completion date: June 1, 2025
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Inclusion Criteria:

• Participation in and completion of MINDS parent study procedures. The inclusion criteria for the MINDS parent study consists of ACHD patients aged 18 - 30 years with moderate and severely complex CHD.

Exclusion Criteria:

• Individuals with mild complexity lesions;
• Individuals with MRI contraindications will be excluded from study participation.

Contraindications include, but are not limited, to:

• Pregnancy or breast feeding
• Claustrophobia or inability to lie still for an extended period
• Implantable device (i.e., pacemaker; defibrillator; ferromagnetic aneurysm clips; cochlear implant; gastric reflux device; internal insulin pump; pacing leads; neurostimulation system) that cannot be cleared for scanning at 3T
• Foreign body (i.e., metallic splinter in the eye; bullet or grenade fragments)
• Braces or orthodontic appliances that cannot be removed prior to scanning and/or cannot be cleared for scanning at 3T
• Individuals who are unable to participate in the informed consent process or complete the study questionnaire will also be excluded from participation.

Related Conditions & MeSH terms

• Adult Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

Other:
• MRI
Magnet Resonance Imaging of the Brain without Contrast

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	University of Utah	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
University of Pittsburgh	Boston Children's Hospital, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (7)

Cohen S, Earing MG. Neurocognitive Impairment and Its Long-term Impact on Adults With Congenital Heart Disease. Prog Cardiovasc Dis. 2018 Sep-Oct;61(3-4):287-293. doi: 10.1016/j.pcad.2018.08.002. Epub 2018 Aug 15. — View Citation

Daliento L, Mapelli D, Russo G, Scarso P, Limongi F, Iannizzi P, Melendugno A, Mazzotti E, Volpe B. Health related quality of life in adults with repaired tetralogy of Fallot: psychosocial and cognitive outcomes. Heart. 2005 Feb;91(2):213-8. doi: 10.1136/hrt.2003.029280. — View Citation

Ilardi D, Ono KE, McCartney R, Book W, Stringer AY. Neurocognitive functioning in adults with congenital heart disease. Congenit Heart Dis. 2017 Mar;12(2):166-173. doi: 10.1111/chd.12434. Epub 2016 Dec 13. — View Citation

Klouda L, Franklin WJ, Saraf A, Parekh DR, Schwartz DD. Neurocognitive and executive functioning in adult survivors of congenital heart disease. Congenit Heart Dis. 2017 Jan;12(1):91-98. doi: 10.1111/chd.12409. Epub 2016 Sep 21. — View Citation

Murphy LK, Compas BE, Reeslund KL, Gindville MC, Mah ML, Markham LW, Jordan LC. Cognitive and attentional functioning in adolescents and young adults with Tetralogy of Fallot and d-transposition of the great arteries. Child Neuropsychol. 2017 Jan;23(1):99-110. doi: 10.1080/09297049.2015.1087488. Epub 2015 Sep 20. — View Citation

Utens EM, Bieman HJ, Verhulst FC, Meijboom FJ, Erdman RA, Hess J. Psychopathology in young adults with congenital heart disease. Follow-up results. Eur Heart J. 1998 Apr;19(4):647-51. doi: 10.1053/euhj.1997.0824. — View Citation

Utens EM, Verhulst FC, Erdman RA, Meijboom FJ, Duivenvoorden HJ, Bos E, Roelandt JR, Hess J. Psychosocial functioning of young adults after surgical correction for congenital heart disease in childhood: a follow-up study. J Psychosom Res. 1994 Oct;38(7):745-58. doi: 10.1016/0022-3999(94)90027-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain Injury	Vascular-related brain injury (cortical infarcts, hemosiderin lesions, and white matter hyperintensity)	At time of MRI