Validation of Circulating Endothelial Cells and Microparticles in Youth

Bariatric Surgery Candidate Clinical Trial

Official title:

Validation of Circulating Endothelial Cells and Microparticles in Youth

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01508598
• Other study ID #: 1108M02842
• Status: Terminated
• Start date: February 2012
• Est. completion date: January 2, 2018

Study information

• Verified date: August 2020
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 390
• Est. completion date: January 2, 2018
• Est. primary completion date: January 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

Inclusion Criteria:

• Age 8-17 years old

• Currently scheduled for elective bariatric surgery

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Bariatric Surgery Candidate
• Childhood Obesity
• Pediatric Obesity

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 12-months		Baseline and 12-months
Secondary	Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 12-months		Baseline and 12 Months
Secondary	Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 12-months		Baseline and 12 Months
Secondary	Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 12-months		Baseline and 12 Months
Secondary	Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 6-months		Baseline and 6-Months
Secondary	Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 6-months		Baseline and 6-Months
Secondary	Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 6-months		Baseline and 6-Months
Secondary	Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 6-months		Baseline and 6-Months