Metabolism of Fibrinogen and Apolipoprotein B-100 in Childhood Obesity and Cardiovascular Disease

NCT02613741 | Completed

• 2 other identifiers: C.20.88400030342B
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

Since obesity and plasma fibrinogen levels are important CVD risk factors in the adults, and since childhood obesity is a major risk factor for adult obesity and also because it is not established whether or not this is due to an increase in the FSR of fibrinogen, the investigators set up the studies with the following specific aims:

1. 1.To investigate the metabolism of fibrinogen and VLDL apoB-100, CVD risk factors, in childhood obesity by measuring their fractional synthetic rate (FSR) compared to lean age and sex matched controls
2. 2.To determine the outcome of a three month non-pharmacological intervention (physical exercise combined with controlled diet) to reduce weight on the FSR of fibrinogen and apoB-100
3. 3.To determine the relationship between FSR of fibrinogen and IL-6 in obese children and its potential implications on CVD before and after the non-pharmacological intervention
4. 4.To determine other CVD risk factors, PAI-1 levels, D-Dimer concentration, homocysteine, insulin, free fatty acid, HDL \& LDL cholesterol and blood pressure in response to weight reduction (as consequence of a combined program of diet and exercise).

Conditions

Obesity; Cardiovascular Disease

Outcome Measures

Primary Outcomes (3)

• Protein turnover

  Stable isotope mass spectrometry

  12 weeks

• Fractional synthesis rate of fibrinogen

  Stable isotope mass spectrometry

  12 weeks

• Fibrinogen

  Plasma concentration measured by nephelometry

  12 weeks

Secondary Outcomes (2)

• Fat mass

  12 weeks

• Fat free mass

  12 weeks

Study Arms (2)

Intervention

EXPERIMENTAL

12 weeks of lifestyle-based physical activity intervention

Other: Lifestyle-based physical activity

Control

NO INTERVENTION

12 weeks of no intervention

Interventions

Lifestyle-based physical activity OTHER

Obese subjects will undergo a randomized physical activity-based weight reduction program (12 weeks). The lifestyle intervention will be determined based on an initial evaluation of each subjects' energy expenditure (by indirect calorimetry). Caloric intake will be set to elicit the loss of 1 to 1.5 lbs/week. The subjects and the family will meet with a dietitian once/week for 12 weeks. The intervention group will undergo an aerobic exercise program 3 times/week. The duration of exercise will be progressively increased from 20 to 45 minutes/session. The subjects will keep daily record of exercise activity and food intake. Interventions will be monitored during the subjects' weekly visit with the research group and they will be given counseling to stick to the intervention program.

Intervention

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Obese: BMI ≥30 kg/m2
• Lean (controls): BMI ≤ 25 kg/m2) age 14 to 18 years and Tanner stage matched
• Ability to understand and cooperate with the procedures
• Signed informed consent from subjects and parents

You may not qualify if:

• Medications such as Beta-adrenergic blockers, steroids and other drugs known to affect protein metabolism
• Heart disease
• Chronic liver disease
• Chronic renal disease
• Active malignancy
• Alcoholism or drug abuse
• Anemia
• Inter-current illness over the 7 days before the study
• Surgery in the past 3 months

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Related Publications (8)

• Balagopal P, Bayne E, Sager B, Russell L, Patton N, George D. Effect of lifestyle changes on whole-body protein turnover in obese adolescents. Int J Obes Relat Metab Disord. 2003 Oct;27(10):1250-7. doi: 10.1038/sj.ijo.0802388.

  PMID: 14513074 RESULT

• Balagopal P, George D, Patton N, Yarandi H, Roberts WL, Bayne E, Gidding S. Lifestyle-only intervention attenuates the inflammatory state associated with obesity: a randomized controlled study in adolescents. J Pediatr. 2005 Mar;146(3):342-8. doi: 10.1016/j.jpeds.2004.11.033.

  PMID: 15756217 RESULT

• Balagopal P, George D, Yarandi H, Funanage V, Bayne E. Reversal of obesity-related hypoadiponectinemia by lifestyle intervention: a controlled, randomized study in obese adolescents. J Clin Endocrinol Metab. 2005 Nov;90(11):6192-7. doi: 10.1210/jc.2004-2427. Epub 2005 Aug 30.

  PMID: 16131584 RESULT

• Balagopal P, Graham TE, Kahn BB, Altomare A, Funanage V, George D. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. J Clin Endocrinol Metab. 2007 May;92(5):1971-4. doi: 10.1210/jc.2006-2712. Epub 2007 Mar 6.

  PMID: 17341558 RESULT

• Balagopal P, George D, Sweeten S, Mann KJ, Yarandi H, Mauras N, Vaughan DE. Response of fractional synthesis rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children. J Thromb Haemost. 2008 Aug;6(8):1296-303. doi: 10.1111/j.1538-7836.2008.03037.x. Epub 2008 May 26.

  PMID: 18507721 RESULT

• Balagopal PB, Gidding SS, Buckloh LM, Yarandi HN, Sylvester JE, George DE, Funanage VL. Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study. Obesity (Silver Spring). 2010 Sep;18(9):1747-53. doi: 10.1038/oby.2009.498. Epub 2010 Jan 21.

  PMID: 20094040 RESULT

• Lovely R, Hossain J, Ramsey JP, Komakula V, George D, Farrell DH, Balagopal PB. Obesity-related increased gamma' fibrinogen concentration in children and its reduction by a physical activity-based lifestyle intervention: a randomized controlled study. J Pediatr. 2013 Aug;163(2):333-8. doi: 10.1016/j.jpeds.2013.01.004. Epub 2013 Feb 14.

  PMID: 23415619 RESULT

• Cosentino RG, Churilla JR, Josephson S, Molle-Rios Z, Hossain MJ, Prado WL, Balagopal PB. Branched-chain Amino Acids and Relationship With Inflammation in Youth With Obesity: A Randomized Controlled Intervention Study. J Clin Endocrinol Metab. 2021 Oct 21;106(11):3129-3139. doi: 10.1210/clinem/dgab538.

  PMID: 34286837 DERIVED

MeSH Terms

Conditions

Obesity; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Babu Balagopal, PhD

  Nemours Children's Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Biomedical Analysis Laboratory

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 24, 2015
• Study Start: January 1, 2001
• Primary Completion: January 1, 2004
• Study Completion: December 1, 2020
• Last Updated: October 14, 2022

Record last verified: 2022-10