Mitochondrial Function in Pediatric Obesity

Obesity Clinical Trial

Official title:

Mitochondrial Function in Pediatric Obesity

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00577174
• Other study ID #: 1K23DK080658
• Secondary ID: 2006p001067, Par
• Status: Active, not recruiting
• Phase: N/A
• First received: December 18, 2007
• Last updated: April 27, 2012
• Start date: June 2007
• Est. completion date: October 2012

Study information

• Verified date: April 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The prevalence of pediatric obesity is increasing at an unprecedented rate. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus. However, the cause of insulin resistance remains an area of scientific interest. The study of type 2 diabetes in children is limited by the lack of a non-invasive method to evaluate insulin resistance. Recent studies have suggested that mitochondrial dysfunction is associated with, and perhaps predictive of insulin resistance in adult relatives of individuals with type 2 diabetes. Mitochondria generate energy in muscle tissue through the production of ATP, and are important in the metabolism of both glucose and fat. This study evaluates a novel, non invasive, safe method for predicting insulin resistance and diabetes in children using a magnetic resonance imaging (MRI) based technique to measure mitochondrial function. We propose to investigate mitochondrial function and glucose metabolism in obese and non-obese children in early, mid and late puberty. Analyses will be conducted to investigate the presence of mitochondrial dysfunction in obese children, to evaluate the contribution of mitochondrial dysfunction to insulin resistance, and to determine the contribution of pubertal status to mitochondrial dysfunction and insulin resistance. The successful completion of this study would provide evidence to support the hypothesis that mitochondrial dysfunction plays a role in insulin resistance and diabetes in children. In addition, it would provide a new technique for the prediction of disease states and perhaps lead to the development of preventative therapeutics for insulin resistance and type 2 diabetes in children.

We hypothesize that mitochondrial dysfunction will mirror the progression of insulin resistance and precede and predict abnormal glucose metabolism in a population with pediatric obesity

Description:

Aim I: A cross sectional study to evaluate baseline mitochondrial function in obese children compared to non-obese children. Determine whether children with pediatric obesity have impaired mitochondrial function based on 31P magnetic resonance spectroscopy when compared to healthy non-obese control children.Examine the relationship between mitochondrial function and insulin resistance in obese and non-obese children. Determine the impact of pubertal stage on mitochondrial function in obese and non-obese children.

Aim II:A prospective evaluation to determine in a longitudinal cohort study the timing and relationship of mitochondrial dysfunction to the development of insulin resistance in prepubertal/early pubertal obese children compared to prepubertal/early pubertal non-obese children. Determine in a longitudinal cohort study if obese children with mitochondrial dysfunction develop greater insulin resistance and/or impaired glucose tolerance at an earlier time point. Evaluate the relationship of obesity, timing of puberty and related changes in hormone levels to mitochondrial function and the development of insulin resistance and/or impaired glucose tolerance in longitudinal analyses.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: October 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 8 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Girls and boys ages 8 to 18 years old

2. Non-obese cohort: body mass index less than 75th percentile for age

3. Obese cohort: body mass index more than 95th percentile for age

Exclusion Criteria:

1. Underlying medical problem with potential to affect growth, pubertal development or glucose homeostasis

2. Chronic medical therapy with glucocorticoids, growth hormone, estrogen, progesterone, testosterone, or other medications with the potential to alter growth, pubertal development or glucose homeostasis within the proceeding 6 months

3. Personal history of diabetes

4. Family history of diabetes in first degree relative

5. Inability to have MRI scan performed due to metal prosthesis or implant

Study Design

Observational Model: Case Control

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity
• Pediatric Obesity

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Children's Hospital Boston, Lawson Wilkins Pediatric Endocrine Society, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Fleischman A, Kron M, Systrom DM, Hrovat M, Grinspoon SK. Mitochondrial function and insulin resistance in overweight and normal-weight children. J Clin Endocrinol Metab. 2009 Dec;94(12):4923-30. doi: 10.1210/jc.2009-1590. Epub 2009 Oct 21. — View Citation

Fleischman A, Makimura H, Stanley TL, McCarthy MA, Kron M, Sun N, Chuzi S, Hrovat MI, Systrom DM, Grinspoon SK. Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle-aged adults. J Clin Endocrinol Metab. 2010 — View Citation

McCormack SE, McCarthy MA, Farilla L, Hrovat MI, Systrom DM, Grinspoon SK, Fleischman A. Skeletal muscle mitochondrial function is associated with longitudinal growth velocity in children and adolescents. J Clin Endocrinol Metab. 2011 Oct;96(10):E1612-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine whether children with pediatric obesity have impaired mitochondrial function based on 31P magnetic resonance spectroscopy when compared to healthy non-obese control children		4 years	No
Primary	Examine the relationship between mitochondrial function and insulin resistance in obese and non-obese children		four years	No
Secondary	Determine the impact of pubertal stage, dietary intake, activity recall, inflammatory markers and metabolic markers on mitochondrial function in obese and non-obese children		four years	No
Secondary	Evaluate the relationship of obesity, timing of puberty and related changes in hormone levels to mitochondrial function and the development of insulin resistance and/or impaired glucose tolerance in longitudinal analyses		four years	No