Validation of Circulating Endothelial Cells and Microparticles in Youth

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01508598
First received: December 13, 2011
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

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.


Condition
Childhood Obesity
Bariatric Surgery Candidate

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Validation of Circulating Endothelial Cells and Microparticles in Youth

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 12-months [ Time Frame: Baseline and 12-months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 12-months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 12-months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 12-months [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Circulating Endothelial Cell (CEC) VCAM Expression at 6-months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Circulating Endothelial Cell (CEC) Enumeration at 6-months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Endothelial Microparticle (EMP) VCAM Expression at 6-months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Endothelial Microparticle (EMP) Enumeration at 6-months [ Time Frame: Baseline and 6-Months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

10 mL of blood serum and 5 mL of blood plasma will be frozen in long-term storage for future study analyses and use. 8 mL of urine will be frozen in long-term storage for future study analyses and use.


Estimated Enrollment: 32
Study Start Date: February 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Thirty-two children and adolescents, who are currently scheduled to undergo elective bariatric surgery.

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • None
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01508598

Contacts
Contact: Cameron E Naughton, M.P.A. 612-625-3623 naug0009@umn.edu

Locations
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Cameron E Naughton, M.P.A.    612-625-3623    naug0009@umn.edu   
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Aaron S Kelly, Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01508598     History of Changes
Other Study ID Numbers: 1108M02842
Study First Received: December 13, 2011
Last Updated: September 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Pediatric
Obesity
Bariatric surgery
Cardiovascular disease

Additional relevant MeSH terms:
Obesity
Pediatric Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on October 01, 2014