Complement and Cardiovascular Risk in Adolescents (CCRIA)

This study evaluates how genetic variations in complement, a part of the immune system, affect cardiovascular risk in adolescents.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Type 2 Diabetes

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
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy adolescents

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Healthy Adolescents; Healthy non Hispanic white adolescents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complement C3 Genotype	Genetic C3F genotype allele presence	Baseline
C4 Copy Number	C4A or C4B gene copy numbers	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI	Body mass index	Baseline
Waist Circumference	Waist circumference at narrowest point	Baseline
Body Fat	Percent body fat BodPod	Baseline
Endothelial Function	reactive hyperemia response to upper arm occlusion	8 min
Vascular Stiffness	augmentation index of reflected blood pressure wave	baseline
Endothelin 1		baseline
Inflammation	IL6	baseline
Clotting	PAI1	baseline
Insulin Sensitivity	Oral glucose tolerance test	baseline

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: American Heart Association

Publications and helpful links

General 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;34(5):599-605. doi: 10.1515/jpem-2020-0619. Print 2021 May 26.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: June 29, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (Estimate): July 1, 2016

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: insulin sensitivity; Complement; adolescents; inflammation; endothelial function
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: Peds34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Clinical Trials.gov