Complement and Cardiovascular Risk in Adolescents (CCRIA)

• ClinicalTrials.gov Identifier: NCT02821104
• Recruitment Status: Completed
• First Posted: July 1, 2016
• Last Update Posted: March 15, 2019
• Sponsor: Ohio State University
• Collaborator: American Heart Association
• Information provided by (Responsible Party): Robert Hoffman, Ohio State University

Study Description

Brief Summary:

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

Condition or disease
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 Design

• Study Type: Observational
• Actual Enrollment: 77 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Complement and Cardiovascular Risk in Adolescents
• Study Start Date: June 2016
• Actual Primary Completion Date: June 30, 2018
• Actual Study Completion Date: June 30, 2018

Groups and Cohorts

Group/Cohort
Healthy Adolescents

Outcome Measures

Primary Outcome Measures :

1. Complement C3 genotype [ Time Frame: Baseline ]
   Genetic variants including A>G polymorphisms at rs11569562 and/or rs2250656,
2. C4 copy number [ Time Frame: Baseline ]
   C4A or C4B gene copy numbers

Secondary Outcome Measures :

1. Body mass [ Time Frame: Baseline ]
   BMI
2. Waist circumference [ Time Frame: Baseline ]
   Waist circumference
3. Body fat [ Time Frame: Baseline ]
   Percent body fat BodPod
4. endothelial function [ Time Frame: baseline ]
   reactive hyperemia
5. Vascular stiffness [ Time Frame: baseline ]
   augmentation index
6. endothelin 1 [ Time Frame: baseline ]
7. inflammation [ Time Frame: baseline ]
   IL6 and Crp
8. clotting [ Time Frame: baseline ]
   fibrinogen and PAI1
9. insulin sensitivity [ Time Frame: baseline ]
   Oral glucose tolerance test

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Healthy adolescents

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

Contacts and Locations

Locations

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Ohio State University

American Heart Association

More Information

• Responsible Party: Robert Hoffman, Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT02821104
• Other Study ID Numbers: Peds34
• First Posted: July 1, 2016
• Last Update Posted: March 15, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Clinical Trials.gov

Keywords provided by Robert Hoffman, Ohio State University:

Complement; endothelial function; insulin sensitivity; adolescents; inflammation

Additional relevant MeSH terms:

Cardiovascular Diseases