Bioenergetics and Metabolism in Pediatric Populations

Obesity Clinical Trial

Official title:

Bioenergetics and Metabolism in Pediatric Populations

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03323294
• Other study ID #: BMPP
• Secondary ID: 2061641P20GM1090
• Status: Active, not recruiting
• Start date: October 18, 2017
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2023
• Source: Arkansas Children's Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators want to learn more about obesity, the development of insulin resistance, and Type 2 Diabetes in children. The investigators will do this through collecting information about children's health and conducting experiments on a variety of samples.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 175
• Est. completion date: December 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

• Age 5-9 years and Tanner stage as reported by parent no greater than stage 1 OR Age 5 years - 17 years 5 months, diagnosed with type 2 diabetes mellitus or insulin resistance

• Either healthy lean (BMI= 5th percentile and <85th percentile for age/sex) or obese (BMI = 95th percentile for age/sex)

• For those with BMI= 95th percentile for age/sex, parental verbal confirmation will be obtained that the child had a history of BMI= 95th percentile for age/sex for at least six months prior to study enrollment

Exclusion criteria:

• Genetic or physical conditions impacting mobility over past year as determined by the Principal Investigator (PI)

• Having known chronic illnesses/disorders that may independently affect study outcome measures: type 1 diabetes mellitus, neurologic (e.g. epilepsy), developmental (developmental delay, autism spectrum disorder), endocrine (thyroid, Cushing's), hepatic, autoimmune, cardiac and renal disorders. Also, chronic lung disorders except well controlled asthma that does not require permanent use of inhaled/oral steroids

• Taking any of the following medications that can affect study outcome: antipsychotics, thyroid hormone replacement therapy, inhaled/oral steroids, insulin, anabolic drugs (growth hormone replacement therapy and oxandrolone) and stimulants

• BMI<5th percentile for age/sex (classified as underweight based on Centers for Disease Control and Prevention growth charts)

• Subjects determined ineligible by the PI.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Resistance
• Obesity
• Type 2 Diabetes Mellitus

Locations

Country	Name	City	State
United States	Arkansas Children's Hospital	Little Rock	Arkansas

Sponsors (4)

Lead Sponsor	Collaborator
Arkansas Children's Hospital Research Institute	National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH), University of Arkansas

Country where clinical trial is conducted

United States, 

References & Publications (35)

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Kramer PA, Chacko BK, Ravi S, Johnson MS, Mitchell T, Darley-Usmar VM. Bioenergetics and the oxidative burst: protocols for the isolation and evaluation of human leukocytes and platelets. J Vis Exp. 2014 Mar 27;(85):51301. doi: 10.3791/51301. — View Citation

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Paltoglou G, Fatouros IG, Valsamakis G, Schoina M, Avloniti A, Chatzinikolaou A, Kambas A, Draganidis D, Mantzou A, Papagianni M, Kanaka-Gantenbein C, Chrousos GP, Mastorakos G. Antioxidation improves in puberty in normal weight and obese boys, in positive association with exercise-stimulated growth hormone secretion. Pediatr Res. 2015 Aug;78(2):158-64. doi: 10.1038/pr.2015.85. Epub 2015 May 4. — View Citation

Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8466-71. doi: 10.1073/pnas.1032913100. Epub 2003 Jun 27. — View Citation

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Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, Goodpaster BH, Ruderman NB, Kelley DE. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E49-58. doi: 10.1152/ajpendo.00317.2009. Epub 2009 Nov 3. — View Citation

Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes. 2005 Jan;54(1):8-14. doi: 10.2337/diabetes.54.1.8. — View Citation

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Santillan LD, Moyano M, Frau M, Flores O, Siewert S, Zirulnick F, Ramirez DC, Gimenez MS. Reduced blood nrf-2 mRNA in local overweight boys at risk of metabolic complications: a study in San Luis City, San Luis, Argentina. Metab Syndr Relat Disord. 2013 Oct;11(5):359-65. doi: 10.1089/met.2012.0155. Epub 2013 Jun 28. — View Citation

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Tyrrell DJ, Bharadwaj MS, Jorgensen MJ, Register TC, Molina AJ. Blood cell respirometry is associated with skeletal and cardiac muscle bioenergetics: Implications for a minimally invasive biomarker of mitochondrial health. Redox Biol. 2016 Dec;10:65-77. doi: 10.1016/j.redox.2016.09.009. Epub 2016 Sep 21. — View Citation

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Vehapoglu A, Turkmen S, Goknar N, Ozer OF. Reduced antioxidant capacity and increased subclinical inflammation markers in prepubescent obese children and their relationship with nutritional markers and metabolic parameters. Redox Rep. 2016 Nov;21(6):271-80. doi: 10.1080/13510002.2015.1133035. Epub 2016 Feb 19. — View Citation

Vincent HK, Innes KE, Vincent KR. Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diabetes Obes Metab. 2007 Nov;9(6):813-39. doi: 10.1111/j.1463-1326.2007.00692.x. — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Altered circulating blood cell bioenergetics	The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will exhibit altered circulating blood cell bioenergetics.	After completion of all study visits, approximately 2 years.
Primary	Oxidized plasma redox state	The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will exhibit a more oxidized plasma redox state.	After completion of all study visits, approximately 2 years.
Primary	Alterations in resting energy expenditure	The investigators hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will be associated with alterations of decreased resting energy expenditure.	After completion of all study visits, approximately 2 years.
Primary	Alterations in fatty acid oxidation	We hypothesize that when compared to normal weight or obese insulin sensitive children, obese insulin resistant children will be associated with alterations of impaired fatty acid oxidation (FAO).	After completion of all study visits, approximately 2 years.
Primary	Poor oxidative capacity	The investigators hypothesize that poor oxidative capacity over time may distinguish between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes.	After completion of all study visits, approximately 2 years.
Primary	Predicting Type 2 Diabetes development	The investigators hypothesize that poor oxidative capacity over time may be predictive of Type 2 Diabetes development.	After completion of all study visits, approximately 2 years.
Primary	Bioenergetics in Type 2 Diabetes with metformin	The investigators hypothesize that the change in bioenergetics will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care.	6 months
Primary	Resting Energy Expenditure in Type 2 Diabetes with metformin	The investigators hypothesize that the change in resting energy expenditure will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care.	6 months
Primary	Fatty Acid Oxidation in Type 2 Diabetes with metformin	The investigators hypothesize that the change in fatty acid oxidation will be improved in obese Type 2 Diabetes children at 6 months of metformin therapy that will be prescribed as part of their clinical care.	6 months