Chronotropic Incompetence During Exercise in Obese Adolescents: Clinical Implications and Pathophysiology (CICO)

Chronotropic Incompetence During Exercise and Relations With Development of Cardiovascular Disease in Obese Adolescents

A reduction in peak heart rate (HR) and suppressed HR response during exercise is highly prevalent in obese populations. This phenomenon is also known as chronotropic incompetence (CI). In adult obese individuals, CI is independently related to elevated risk for major adverse cardiovascular events and premature death. Despite the established association between CI and prognosis in adult populations, the prognostic relevance of CI in adolescents with obesity has however deserved no attention, but is important. CI during exercise testing may indicate various, yet undetected anomalies, such as altered blood catecholamine and/or potassium concentrations during exercise, structural myocardial abnormalities or ventricular stiffness, impaired baroreflex sensitivity and cardiovascular autonomic dysfunction, atherosclerosis, or cardiac electrophysiological anomalies, which all have been detected in obese children and adolescents. However, whether CI during exercise testing may be a sensitive and specific indicator for these anomalies in obese adolescents has not been studied yet. In addition, the exact physiology behind obesity and development of heart disease remains to be studied in greater detail in obese adolescents. In this project, we examine the prevalence of CI (during maximal cardiopulmonary exercise testing, CPET) in 60 obese adolescents (aged 12-16 years) vs. 60 lean adolescents, and study the association between CI and changes in CPET parameters, lactate, catecholamine and potassium concentrations during CPET, biochemical variables, and cardiac electrophysiology (by ECG recording). In addition, the relation between CI and cardiac function (echocardiography) will be examined in a subgroup (29 lean and 29 obese) of these adolescents. In this regard, the diagnostic value of HR (responses) during maximal exercise testing will be clarified in obese adolescents, and the physiology behind the elevated risk for heart disease in obese adolescents can be explored.

Study Overview

• Status: Completed
• Conditions: Obesity; Adolescent Obesity
• Intervention / Treatment: Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 16 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 12-16 years
• obese or lean (based on extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity)
• Parental permission

Exclusion Criteria:

- Chronic cardiovascular, renal, pulmonary and orthopedic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Obese adolescents	Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET
OTHER: Lean adolescents	Other: the prevalence of chronotropic incompetence CI during maximal cardiopulmonary exercise testing, CPET

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate (HR)	Assessed using a 12-lead ECG device	day 1
Ventilatory function	Determined during maximal cardiopulmonary exercise testing.	day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
weight		day 1
height		day 1
body composition		day 1
PAQ-A (Physical Activity Questionaire for Adolescents)	physical activity determined using the validated Dutch physical activity questionnaire for adolescents	day1
Tanner scale	Puberty stage (ranging from 1 to 5) will be assessed in all participants by the pediatric endocrinologist using Tanner staging criteria. Boys - development of external genitalia Girls - breast development Boys and girls - pubic hair	day 1
Plasma glucose	blood analyses	day 1
iron	blood analyses	day 1
aspartate aminotransferase	blood analyses	day 1
alanine aminotransferase	blood analyses	day 1
gamma-glutamyl transpeptidase	blood analyses	day 1
alkaline phosphatase	blood analyses	day 1
uric acid	blood analyses	day 1
calcium	blood analyses	day 1
blood total cholesterol	blood analyses	day 1
high-density lipoprotein cholesterol	blood analyses	day 1
low-density lipoprotein cholesterol	blood analyses	day 1
proteins	blood analyses	day 1
triglyceride concentrations	blood analyses	day 1
c-reactive proteine	blood analyses	day 1
thyroid-stimulating hormone	blood analyses	day 1
free thyroxine	blood analyses	day 1
cortisol and serum insulin	blood analyses	day 1
serum leptin concentration	blood analyses	day 1
blood haemoglobin	blood analyses	day 1
haematocrit	blood analyses	day 1
leukocytes	blood analyses	day 1
Echocardiography	Assessment left ventricular structure and systolic and diastolic function	day 1

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Jessa Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): May 1, 2017
• Study Completion (ACTUAL): August 31, 2019

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (ACTUAL): May 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity
• Other Study ID Numbers: CICO-001

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