Clinical trial NCT01508598: Validation of Circulating Endothelial Cells and Microparticles in Youth
Official title: Validation of Circulating Endothelial Cells and Microparticles in Youth
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Childhood Obesity
Bariatric Surgery Candidate
Keywords: Pediatric
Obesity
Bariatric surgery
Cardiovascular disease
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2012-01-12
Enrollment: 390
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Thirty-two children and adolescents, who are currently scheduled to undergo elective bariatric surgery.

Brief summary: Identification and validation of early chronic disease biomarkers in children is of paramount importance especially in the burgeoning arena of pediatric obesity research. Despite the presence of risk factors, few obese children develop overt cardiovascular disease (CVD) early in life. However, because CVD is a cumulative process occurring over time, identifying the earliest signs in order to intervene sooner may have a large impact on slowing its progression. Endothelial activation is one of the earliest detectable signs of the beginnings of CVD. However, accurately quantifying endothelial health in children has proven to be a major challenge. Direct measures of endothelial cell biology, such as circulating endothelial cells (CEC) and endothelial microparticles (EMP), have been extensively studied in adults and are associated with vascular diseases, CVD risk factors, and CVD events. Despite being well-validated in adults, CEC and EMP have not been formally evaluated as disease biomarkers in children and adolescents. Pediatric obesity is an ideal condition in which to validate CEC and EMP as disease biomarkers since adiposity in childhood is associated with CVD, type 2 diabetes mellitus, and premature death, later in life. The investigators primary focus in this study will be the evaluation of CEC and EMP as biomarkers of CVD risk and whether substantial changes in weight affect these biomarkers. The investigators propose to evaluate the change in levels of CEC and EMP in response to substantial weight loss in 32 adolescents with extreme obesity undergoing elective, clinically-indicated bariatric surgery.

Detailed description: Identification and validation of early chronic disease biomarkers in children is of paramount importance especially in the burgeoning arena of pediatric obesity research. Despite the presence of risk factors, few obese children develop overt CVD early in life. However, the pathologic process of CVD begins in the first two decades of life, particularly in the presence of obesity. Because CVD is a cumulative process occurring over time, identifying the earliest signs in order to intervene sooner may have a large impact on slowing its progression. The challenge is identifying which obese youth have early vascular problems. Looking to the vascular endothelium for biomarkers of damage is a reasonable approach because of its prominent role in the origins of atherosclerosis. Endothelial activation is one of the earliest detectable signs of the beginnings of CVD and predicts subsequent atherosclerosis and future cardiovascular events. However, accurately quantifying endothelial health in children has proven to be a major challenge.

Brachial artery FMD is the most commonly-used method to quantify endothelial health in children. However, this technique is not widely applicable, even in the research setting, because it requires specialized equipment and a highly-trained technician. Moreover, results can be highly variable (especially across sites) due to operator dependence and intra-individual fluctuations in endothelial function. More direct measures of endothelial cell biology, such as CEC and EMP, may offer greater precision in characterizing the state of the endothelium and may be especially useful as risk-prediction biomarkers in youth since they are hallmarks of advanced endothelial cell distress, thereby identifying the highest-risk individuals. CEC and EMP have been extensively studied in adults and are associated with vascular diseases, CVD risk factors, and CVD events. Despite being well-validated in adults, CEC and EMP have not been formally evaluated as disease biomarkers in children and adolescents.

Pediatric obesity is an ideal condition in which to validate CEC and EMP as disease biomarkers since adiposity in childhood is associated with CVD, type 2 diabetes mellitus, and premature death later in life. In particular, extreme obesity is an especially high-risk condition associated with significant co-morbidities. Our primary focus in this study will be the evaluation of CEC and EMP as biomarkers of CVD risk, with a goal of validating CEC and EMP for use as vascular endpoints in pediatric research studies. We propose to evaluate the change in levels of CEC and EMP in response to substantial weight loss in adolescents with extreme obesity undergoing elective, clinically-indicated bariatric surgery.

Specific Aims:

1. Evaluate the effect of substantial weight loss on levels of CEC and EMP in adolescents with extreme obesity.

We hypothesize that levels of CEC and EMP will be significantly reduced following elective, clinically-indicated bariatric surgery in adolescents with extreme obesity. The magnitude of change in CEC and EMP levels will be correlated with the magnitude of weight loss and improvements in CVD risk factors and endothelial function following bariatric surgery.

We will enroll 32 children and adolescents (ages 8-17) who are scheduled for elective bariatric surgery. They will be evaluated prior to their surgery, six months after surgery and twelve months after surgery.

Eligibility criteria: Inclusion Criteria:

* Age 8-17 years old
* Currently scheduled for elective bariatric surgery

Exclusion Criteria:

* None

Primary outcomes:
measure: Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 12-months
timeFrame: Baseline and 12-months
Secondary outcomes:
measure: Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 12-months
timeFrame: Baseline and 12 Months
measure: Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 12-months
timeFrame: Baseline and 12 Months
measure: Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 12-months
timeFrame: Baseline and 12 Months
measure: Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 6-months
timeFrame: Baseline and 6-Months
measure: Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 6-months
timeFrame: Baseline and 6-Months
measure: Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 6-months
timeFrame: Baseline and 6-Months
measure: Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 6-months
timeFrame: Baseline and 6-Months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Aaron S Kelly, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fox CK, Northrop EF, Rudser KD, Ryder JR, Kelly AS, Bensignor MO, Bomberg EM, Bramante CT, Gross AC. Contribution of Hedonic Hunger and Binge Eating to Childhood Obesity. Child Obes. 2021 Jun;17(4):257-262. doi: 10.1089/chi.2020.0177.
citation: Fyfe-Johnson AL, Ryder JR, Alonso A, MacLehose RF, Rudser KD, Fox CK, Gross AC, Kelly AS. Ideal Cardiovascular Health and Adiposity: Implications in Youth. J Am Heart Assoc. 2018 Apr 13;7(8):e007467. doi: 10.1161/JAHA.117.007467.