Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00962806

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pediatric Obesity Insulin Resistance Mitochondrial Dysfunction	Behavioral: Exercise Behavioral: Lifestyle counseling	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity

Study Start Date :

Aug 1, 2009

Anticipated Primary Completion Date :

Jun 1, 2012

Anticipated Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Exercise 8 week intensive exercise group	Behavioral: Exercise 8 weeks of intensive exercise, 60-90 minutes 3 days each week
Other: Control Lifestyle counseling Lifestyle counseling without intensive exercise	Behavioral: Lifestyle counseling Baseline and final visit dietary and activity advice and weekly healthy lifestyle messages

Arm

Intervention/Treatment

Active Comparator: Exercise

8 week intensive exercise group

Behavioral: Exercise

8 weeks of intensive exercise, 60-90 minutes 3 days each week

Other: Control Lifestyle counseling

Lifestyle counseling without intensive exercise

Behavioral: Lifestyle counseling

Baseline and final visit dietary and activity advice and weekly healthy lifestyle messages

Outcome Measures

Primary Outcome Measures

Determine whether intensive exercise improves mitochondrial function by P31 MRS and mitochondrial number by peripheral blood analyses. [2 year]

Secondary Outcome Measures

Determine whether intensive exercise improves metabolic parameters and glucose metabolism. [2 years]
Determine whether intensive exercise improves body composition, by DXA, and intramyocellular fat content, by 1H MRS. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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