Clinical trial NCT00140842: Neuroendocrine Modulation of Metabolic Effects in Overweight Adolescents
Official title: Neuroendocrine Modulation of Metabolic Effects in Overweight Adolescents
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: Obesity, adolescent, ghrelin, growth hormone, cortisol
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2005-09-01
Enrollment: 47
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Obese and normal-weight girls between 12-18 years old

Brief summary: This study will examine hormonal differences in ghrelin and growth hormone in obese and normal weight adolescents and their relationship to body composition and insulin resistance. The study will also investigate the effect of the macronutrient composition of a meal on postprandial ghrelin levels and whether ghrelin responses will predict the degree of hunger and caloric intake at a subsequent meal.

Detailed description: Obesity is an epidemic that is striking people at younger ages than ever before. Obesity is associated with changes in the secretory patterns of several hormones including ghrelin, growth hormone (GH), and insulin, which have not been examined in the adolescent age group. Ghrelin, a primarily gastric hormone, increases appetite and is a GH secretagogue. This study will compare the alteration in secretion of ghrelin and GH in overweight and normal weight adolescent girls through frequent blood sampling and GH stimulation testing with growth hormone releasing hormone and arginine. The relationship between these hormones and insulin resistance, measured by 1H-nuclear magnetic resonance spectroscopy, and body composition, measured by dual energy x-ray absorptiometry and magnetic resonance imaging, will be investigated. This study will also determine the postprandial ghrelin response to test meals that vary by the type of predominant macronutrient, which may predict the degree of hunger and amount of intake at a subsequent meal. Understanding obesity-related changes in ghrelin and GH and their relationship to body composition, insulin resistance, and appetite will help in the development of strategies to reduce complications of obesity.

Eligibility criteria: Inclusion Criteria:

1. Girls 12-18 years of age
2. Obese subjects: BMI higher than the 95th percentile for age and sex
3. Normal-weight controls: BMI from the 15th to the 85th percentiles for age and sex

Exclusion Criteria:

1. History of disorders other than obesity that may affect growth hormone, ghrelin, cortisol, or insulin secretion such as eating disorder, diabetes mellitus, hypertension, thyroid disease, Cushing's syndrome, liver disease, renal failure, or an excess or deficiency of GH or cortisol
2. Medications that could affect glucose and lipid levels or the secretion of growth hormone, ghrelin, insulin, or cortisol such as rhGH, glucocorticoids, and birth control pills
3. Pregnancy
4. Smoking or substance abuse
5. Active dieting
6. Surgical procedures for obesity
7. Dietary restrictions such as bread, dairy, peanut, aspartame, or meat products used in the study
8. Metal implants, including intracranial surgical clips or pacemakers

Primary outcomes:
measure: Peak Growth Hormone (GH) on the GH Stimulation Test
timeFrame: Baseline
Secondary outcomes:
measure: Visceral Adipose Tissue
timeFrame: Baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Madhusmita Misra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Misra M, Tsai PM, Mendes N, Miller KK, Klibanski A. Increased carbohydrate induced ghrelin secretion in obese vs. normal-weight adolescent girls. Obesity (Silver Spring). 2009 Sep;17(9):1689-95. doi: 10.1038/oby.2009.86. Epub 2009 Mar 26.
citation: Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A. Lower growth hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E385-92. doi: 10.1152/ajpendo.00052.2008. Epub 2008 Jun 10.
citation: Russell M, Bredella M, Tsai P, Mendes N, Miller KK, Klibanski A, Misra M. Relative growth hormone deficiency and cortisol excess are associated with increased cardiovascular risk markers in obese adolescent girls. J Clin Endocrinol Metab. 2009 Aug;94(8):2864-71. doi: 10.1210/jc.2009-0380. Epub 2009 May 12.
citation: Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M. Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab. 2010 Mar;95(3):1247-55. doi: 10.1210/jc.2009-1475. Epub 2010 Jan 15.