Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

Insulin Resistance Clinical Trial

Official title:

Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00962806
• Other study ID #: DK084118
• Secondary ID: Partners IRB: 20
• Status: Active, not recruiting
• Phase: N/A
• First received: August 18, 2009
• Last updated: April 25, 2012
• Start date: August 2009
• Est. completion date: December 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: Interventional

Clinical Trial Summary

Obesity and type 2 diabetes are occurring at epidemic rates in the United States and worldwide. The global burden of diabetes is estimated to double over the next 25 years. Obese children are at risk for the development of insulin resistance, relative insulin deficiency and type 2 diabetes mellitus (DM). The prevention of type 2 DM is hindered by the lack of a non-invasive predictive test, knowledge as to individual risk and effective preventative measures. There is increasing evidence that alterations in mitochondria contribute to the development of diabetes in humans. Therefore, it is important to explore mitochondrial dysfunction as a potential predictor of diabetes in children and a potential target for prevention. The aims of the proposed protocol are to determine whether an intensive exercise intervention can improve mitochondrial function in children identified as having mitochondrial dysfunction and insulin resistance. The use of a non-invasive imaging technique will allow for a functional in vivo assessment of mitochondrial activity. The investigators propose the investigation of an intensive exercise protocol designed to improve mitochondrial function in children who are insulin resistant and have documented mitochondrial dysfunction by magnetic resonance spectroscopy. The study is designed to investigate the plasticity of abnormal mitochondrial function in high risk children. In summary, the proposed projects will investigate mitochondrial function as a non-invasive predictive marker for the development of insulin resistance and type 2 diabetes mellitus in children and attempt to modify mitochondrial function with an intensive exercise intervention. The study of mitochondrial dysfunction in children may both identify those at risk for disease and provide a molecular therapeutic target for prevention and treatment.

The investigators hypothesize that children with insulin resistance and mitochondrial dysfunction who are randomized to intensive exercise versus standard lifestyle advice will show improvement in mitochondrial function and insulin sensitivity.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 18 Years

Eligibility

Inclusion Criteria:

• Girls and boys ages 10 to 18 years old

• Body mass index more than 95th percentile for age and gender

• Insulin resistance based on:

• Fasting parameters: Fasting insulin level, HOMA IR

• Oral glucose tolerance testing

• Mitochondrial function > 1 median for normal based on control cohort

Exclusion Criteria:

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

• 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

• Personal history of DM

• Inability to have MRI scan performed due to metal prosthesis or implant

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Mitochondrial Dysfunction
• Obesity
• Pediatric Obesity

Intervention

Behavioral:
• Exercise
8 weeks of intensive exercise, 60-90 minutes 3 days each week
• Lifestyle counseling
Baseline and final visit dietary and activity advice and weekly healthy lifestyle messages

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine whether intensive exercise improves mitochondrial function by P31 MRS and mitochondrial number by peripheral blood analyses.		2 year	No
Secondary	Determine whether intensive exercise improves metabolic parameters and glucose metabolism.		2 years	No
Secondary	Determine whether intensive exercise improves body composition, by DXA, and intramyocellular fat content, by 1H MRS.		2 years	No