Accelerated Aging in Newborns and Adults With Congenital Heart Disease (AccelerAGE)

A Lifespan Perspective on Accelerated Aging in Congenital Heart Disease

Many childhood-onset diseases used to be lethal. Improved life expectancy yield that most patients can survive into adulthood, to date. However, survivors of childhood-onset diseases often develop morbidities that suggest accelerated aging. Indeed, age-related conditions are observed sooner and more frequently in people with childhood-onset diseases. Congenital heart disease (CHD) is a typical example of a childhood-onset disease and is the most common birth defect, comprising a spectrum of mild, moderate and complex heart defects. Recent studies showed that age-related morbidities occur more often and at an earlier age in these patients. The overall goal of this project is to quantify and understand disparities in chronological and biological age over the lifespan in CHD patients.

Study Overview

• Status: Recruiting
• Conditions: Heart Defects, Congenital

Detailed Description

Three main research objectives are proposed:

Objective 1: The investigators will determine the biological age in patients with CHD across the lifespan, using established and novel biomarkers for aging, and assess the disparity with chronological age.

Objective 2: The investigators will identify clinical, behavioral, psychological and social predictors of aging in patients with CHD.

Objective 3: The investigators will investigate the difference in biological-chronological age disparity between patients with CHD and healthy counterparts.

Three studies will be performed to investigate these objectives:

Study 1: Newborns with CHD

- The aim is to (i) compare telomere length in newborns with or without CHD; and (ii) to assess pregnancy-related/clinical and mother-related (behavioral, psychological, social) predictors of telomere length in newborns with CHD.

Study 2: (Young) adults with CHD

- This study aims to (i) compare telomere length in age strata of (young) adults with or without CHD; (ii) to assess clinical, behavioral, psychological, and social predictors of telomere length in patients with CHD; and (iii) to explore the relationship with functional outcomes, such as frailty and cognition.

Study 3: Epigenetic clock in adults with CHD

- This study focusses on (i) assessing the biological age by measuring DNA methylation in mild, moderate and complex heart defects, and (ii) determining if the disparity between biological and chronological age is a function of anatomical complexity and functional status of the patients and (iii) comparing the epigenetic clock of adults with and without CHD.

• Study Type: Observational
• Enrollment (Estimated): 1200

Contacts and Locations

• Study Contact: Name: Philip Moons, PhD, RN; Phone Number: 016/373315; Email: philip.moons@kuleuven.be
• Study Contact Backup: Name: Bo Daelman, MSc; Phone Number: 016/193201; Email: bo.daelman@kuleuven.be

Study Locations

• Belgium
  • Ghent, Belgium
    • Recruiting
    • Ghent University Hospital
    • Contact: Julie De Backer, PhD, MD; Phone Number: 09/3323344; Email: julie.debacker@ugent.be
    • Sub-Investigator: Tijs Tournoy, MD
  • Leuven, Belgium
    • Not yet recruiting
    • University Hospital Leuven
    • Contact: Philip Moons, PhD, RN; Phone Number: 016/373315; Email: philip.moons@kuleuven.be
    • Sub-Investigator: Bo Daelman, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

1. Newborns with CHD and mother
2. Adults with CHD - study 2 For each age stratum 100 patients must be included (Gent and Leuven combined), so a total of 500 patients will be included: 18-24 years of age, 25-34 years of age, 35-44 years of age, 45-54 years of age, ≥ 55 years of age
3. Adults with CHD - study 3 These patients must also be included in study 2. The patients must have the following CHD conditions: isolated arterial septal defect, isolated ventricular septal defect, tetralogy of Fallot, coarctation of the aorta, Fontan operation or systemic right ventricle. Furthermore, they need to be between 30-50 years old.
4. Healthy volunteers Health volunteers of the Red Cross.

Description

1. Newborn with CHD and mother

   Inclusion:

   • Newborns with CHD who are diagnosed and born in UZ Leuven or UZ Gent
   • The mother is able to adequate fill out the questionnaires
   • Informed consent is signed

   Exclusion:

   • The mother does not speak Dutch
   • The heart defect falls within a syndrome condition (e.g., Down syndrome, 22q11 deletion)
   • Very mild heart defects such as a patent foramen ovale, an open ductus of Botalli (no intervention needed), spontaneous closure of ASD/VSD, an isolated mild peripheral pulmonary stenosis

2. Adults with CHD - study 2

   Inclusion:

   • ≥ 18 years of age at the moment of study inclusion
   • Diagnosed with CHD
   • Follow-up at the UZ Leuven or UZ Gent
   • Signed informed consent
   • Physical, cognitive, and language abilities to complete self-report questionnaires/ assessment tests

   Exclusion:

   • Not speaking Dutch
   • Very mild heart defects such as a patent foramen ovale, an open ductus of Botalli (no intervention needed), spontaneous closure of ASD/VSD, an isolated mild peripheral pulmonary stenosis
   • The heart defect falls within a syndrome condition (e.g., Down syndrome, 22q11 deletion)

3. Adults with CHD - study 3

   Inclusion:

   • Included in study 2
   • Between 30-50 years of age at the moment of study inclusion
   • Follow-up at the UZ Leuven or UZ Gent
   • Signed informed consent
   • Physical, cognitive, and language abilities to complete self-report questionnaires/ assessment tests
   • Having one of the following CHD conditions: isolated arterial septal defect, isolated ventricular septal defect, tetralogy of Fallot, coarctation of the aorta, Fontan operation or systemic right ventricle.

   Exclusion

   • Not speaking Dutch
   • The heart defect falls within a syndrome condition (e.g., Downsyndrome, 22q11 deletion)
4. Health volunteers

Inclusion:

• Male or female healthy volunteers of the Red Cross
• Aged 18 - 65 years at the moment of inclusion
• The healthy volunteers must match with the patients included in study 2 based on age and sex
• Signed informed consent
• The requirements of the Red Cross for blood donation are fulfilled

Exclusion:

• Medical history of cardiac, pulmonal, renal or liver disease, chronic anemia, blood clotting disorder
• Not speaking Dutch
• Pregnancy
• Born with a heart condition

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Newborns with CHD and their mothers; Consecutive newborns with CHD (n=100), who are diagnosed and born in the University Hospitals of Leuven and Ghent, are eligible for inclusion. Mothers (n=100) will be asked for participation in the study before delivery and written informed consent will be obtained. Umbilical cord blood of the ENVIRONAGE study (Hasselt University) will be used as a control group.
(Young) adults with CHD - study 2; An age-stratified random sample of (young) adults with CHD, followed-up at the University Hospital of Leuven and the Ghent University Hospital will be included. Age strata for this study are: 18-24y; 25-34y; 35-44y; 45-54y; 55+. In total 500 patients will be included, 100 in each age stratum.
(Young) adults with CHD - study 3; At the University Hospital of Leuven and Ghent University Hospital, patients with selected complex (Fontan operation; Systemic right ventricle), moderate (Tetralogy of Fallot; Coarctation of the aorta), and mild heart defects (isolated atrial septal defect; isolated ventricular septal defect) are eligible. For each type of heart defect 20 patients between the age of 30-50 years are enrolled. The overall sample will comprise 120 patients, who will be part of study 2 as well.
Healthy controls; Data on healthy controls (n=500) will be retrieved from blood donors at the blood donation service of the Belgian Red Cross-Flanders. The healthy controls will be matched to the included adult patients (in study 2 and 3) based on sex and age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Telomere length	Telomere length will be measured on umbilical cord blood from newborns and on peripheral blood from adults with and without CHD.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical, behavioral, psychological and social predictors of telomere length	This will be studied by using the life history calendar in adults. In newborns, a pregnancy history calendar and correlation with the maternal telomere length will be used.	Baseline
Frailty as a functional outcome of aging in adults with CHD	The Fried method is used for assessment of frailty and consists of five parts: self-report questions about unintentional weight loss, exhaustion and physical activity, an assessment of weakness performed using a handgrip dynamometer, and a walk test. A patient is considered non-frail, pre-frail and frail if, respectively, 0, 1-2 or 3/more components are present.	Baseline
hsCRP in adults with CHD		Baseline
Fall history as a functional outcome of aging in adults with CHD	A fall history questionnaire will be used.	Baseline
Cognitive impairment as a functional outcome of aging in adults with CHD	The Montréal Cognitive Assessment Screener (MoCA) is used for assessment of cognitive function. The maximum score is 30 points, a score of 26 or higher is considered normal. A lower score indicates a worse cognitive function.	Baseline
Epigenetic clock in adults with and without CHD	This will be examined based on DNA methylation.	Baseline
Retina scan in adults with CHD	This will only be performed on patients included in Leuven	Baseline

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Hasselt University; University Hospital, Ghent
• Investigators: Principal Investigator: Philip Moons, Prof. PhD, Professor in Healthcare Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: December 28, 2022
• First Posted (Actual): December 29, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Aging; Congenital heart disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Cardiovascular Abnormalities; Heart Diseases; Congenital Abnormalities; Heart Defects, Congenital
• Other Study ID Numbers: S66590

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No