Predictive Value of Neurovascular Coupling in Infants With COngenital Heart Disease

Recruiting

• Conditions: Biomarkers; Near-Infrared Spectroscopy; Congenital Heart Disease; Neurodevelopmental Disorders; Electroencephalography
• Interventions: Diagnostic Test: electroencephalography; Diagnostic Test: Near-Infrared Spectroscopy; Diagnostic Test: neuronal cell-free DNA

• Registration Number: NCT06190210
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

Infants with congenital heart disease (CHD) are at increased risk for delayed neurodevelopment. Multiple etiological explanations have been proposed, as there seems to be a multifactorial interplay of both prenatal and perioperative factors. The main goal of this research project is to focus on peri-operative physiological risk factors in infants with CHD which impair functional brain maturation or elicit brain injury, and subsequently creating a risk model and guidelines for standardized developmental follow-up in this population.

PART 1: investigation of cerebral autoregulation and neurovascular coupling The homeostasis in cerebral blood supply regardless of perfusion pressure, is called Cerebral autoregulation (CAR). Neurovascular coupling (NVC) is the phenomenon in which blood supply increases as a result of increased brain activity in a specific area. At different times in the perioperative phase, these regulatory mechanisms will be estimated based on Electroencephalography (EEG) and Near Infrared Spectroscopy (NIRS), in addition to hemodynamic parameters.

PART 2: cell-free DNA (cfDNA) extraction. Non-invasive monitoring of neuronal degeneration can be performed using cfDNA extraction techniques. Serial measurements of neuronal cfDNA will be used to determine whether and when this neuronal damage has occurred.

PART 3: Prognosis and outcome. These risk factors, supplemented with demographic factors and medications administered, will be combined in an Artificial Intelligence-driven model, thus establishing a risk model for neurodevelopmental outcome. This model will be compared to the current standard-of-care, both structural imaging (ultrasound and MRI) and a clinical developmental assessment at 9 and 24 months of age (Bayley Scales of Infant Development-III).

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-01
• Study First Submitted: 2023-12-15
• Study First Submitted QC: 2024-01-02
• Study First Posted: 2024-01-05
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• CHD warranting a first percutaneous or surgical intervention in the first 6 months, including but not limited to transposition of the great arteries (TGA), univentricular heart (UVH), Tetralogy of Fallot (TOF), coarctation of the aorta (CoA), total abnormal pulmonary venous drainage (TAPVU), Common arterial trunc (TA), large patent ductus arteriosus (PDA) or VSD and AVSD for which treatment is necessary within the first 6 months of life.
• Treatment provided at the University Hospitals Leuven.

Exclusion Criteria

• Syndromes or proven genetic conditions which are associated with neurological impairment
• CHD warranting treatment after 6 months of life
• Suspected or proven metabolic diseases
• No parental/guardian consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Congenital heart disease	electroencephalography	Neonates with congenital heart disease necessitating treatment before the age of 6 months, either surgical or through cardiac catheterization
Congenital heart disease	neuronal cell-free DNA	Neonates with congenital heart disease necessitating treatment before the age of 6 months, either surgical or through cardiac catheterization
Congenital heart disease	Near-Infrared Spectroscopy	Neonates with congenital heart disease necessitating treatment before the age of 6 months, either surgical or through cardiac catheterization

Primary Outcome Measures

Name	Time	Method
Brain MRI structural brain abnormalities	+- 1 week postoperative	Incidence of patients with normal brain development vs rate of bleeding/stroke visualized on brain MRI Differences in total brain volume and cerebellar volume in patients with congenital heart disease
Clinical neurological development measured with Bayley Scale of Infant Development	9 months, 24 months	Rate of abnormal clinical neurodevelopment measured with the Bayley Scale of Infant Development (BSID-III): range 50-150, mean 100, SD 15

Trial Locations

Locations (1)

UZ Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium