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Complement and Cardiovascular Risk in Adolescents (CCRIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02821104
Recruitment Status : Completed
First Posted : July 1, 2016
Last Update Posted : March 15, 2019
American Heart Association
Information provided by (Responsible Party):
Robert Hoffman, Ohio State University

Tracking Information
First Submitted Date June 29, 2016
First Posted Date July 1, 2016
Last Update Posted Date March 15, 2019
Study Start Date June 2016
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 30, 2016)
  • Complement C3 genotype [ Time Frame: Baseline ]
    Genetic variants including A>G polymorphisms at rs11569562 and/or rs2250656,
  • C4 copy number [ Time Frame: Baseline ]
    C4A or C4B gene copy numbers
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 30, 2016)
  • Body mass [ Time Frame: Baseline ]
  • Waist circumference [ Time Frame: Baseline ]
    Waist circumference
  • Body fat [ Time Frame: Baseline ]
    Percent body fat BodPod
  • endothelial function [ Time Frame: baseline ]
    reactive hyperemia
  • Vascular stiffness [ Time Frame: baseline ]
    augmentation index
  • endothelin 1 [ Time Frame: baseline ]
  • inflammation [ Time Frame: baseline ]
    IL6 and Crp
  • clotting [ Time Frame: baseline ]
    fibrinogen and PAI1
  • insulin sensitivity [ Time Frame: baseline ]
    Oral glucose tolerance test
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Complement and Cardiovascular Risk in Adolescents
Official Title Complement and Cardiovascular Risk in Adolescents
Brief Summary This study evaluates how genetic variations in complement, a part of the immune system, affect cardiovascular risk in adolescents.
Detailed Description Cardiometabolic diseases usually do not produce significant mortality and morbidity until adulthood. There is clear evidence, however, that these diseases have their origins in childhood and adolescence. With the rising incidence of obesity associated with poorer eating and less physical activity in children and adolescents it is important that the investigators study these diseases early in their course if the investigators are to prevent future cardiometabolic disease. While obesity clearly increases cardiometabolic risk, not all obese subjects are at increased risk; approximately 25-30% of obese adults and adolescents are metabolically healthy. The complement system is key physiological component in controlling inflammation and recent studies have indicated complement plays an important role in increasing obesity and cardiometabolic risk. Adults with proven cardiometabolic disease or at future risk for cardiometabolic disease have increased levels of the complement components C3, C3a-desArg, and C4 compared to healthy, not at risk, control subjects, independent of obesity. Increased C3 or C3a-desArg levels in adolescents are associated with increased cardiometabolic risk independent of obesity. Two specific single nucleotide polymorphisms (SNPs) in the intron for C3, rs11569562 and rs2250656, both with A>G polymorphisms, are associated with increased serum C3 levels, and increases in a variety of cardiovascular risk factors. No one has investigated how C3 polymorphisms affect risk factors in adolescents. The C4 gene has significant copy number variation and increased copy number is associated with increased C4 levels. The relationship of C4 gene copy number to cardiometabolic risk has not been studied in adults or adolescents. The short-term objectives of this study are to explore differences in cardiometabolic risk factors in overweight and obese adolescents with C3 polymorphisms and also to explore how C4 gene copy number variation affects risk factors. The investigators overall hypothesis is that variations in C3 polymorphisms, C4 gene copy number or both will have significant impact on cardiometabolic health in overweight and obese adolescents. Both traditional and nontraditional cardiometabolic risk markers, including measures of body habitus, blood pressure, lipids, vascular function, insulin secretion and sensitivity, inflammation, and clotting will be investigated in 100 overweight and obese adolescents. The investigators proposed study will help us understand the role of complement and its genetics in the development of cardiometabolic risk and in potentially developing genetic biomarkers for adolescents at increased risk.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Probability Sample
Study Population Healthy adolescents
  • Cardiovascular Disease
  • Type 2 Diabetes
Intervention Not Provided
Study Groups/Cohorts Healthy Adolescents
Publications * Hoffman RP, Copenhaver MM, Zhou D, Yu CY. Oral glucose tolerance response curve predicts disposition index but not other cardiometabolic risk factors in healthy adolescents. J Pediatr Endocrinol Metab. 2021 Apr 5. doi: 10.1515/jpem-2020-0619. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: March 13, 2019)
Original Estimated Enrollment
 (submitted: June 30, 2016)
Actual Study Completion Date June 30, 2018
Actual Primary Completion Date June 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Healthy adolescents age 12 to 18 years
  • Medication free for 2 weeks except oral contraceptives in females
  • Non Hispanic white

Exclusion Criteria:

  • Chronic medications except for contraceptives in females.
  • History of autoimmune disease either endocrine or connective tissue type
  • History of hematologic or renal disease, malignancy or other chronic disease
  • Hispanic ethnicity,
  • African-American or Asian race
Sexes Eligible for Study: All
Ages 12 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT02821104
Other Study ID Numbers Peds34
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: Clinical
Responsible Party Robert Hoffman, Ohio State University
Study Sponsor Ohio State University
Collaborators American Heart Association
Investigators Not Provided
PRS Account Ohio State University
Verification Date March 2019