Neuroendocrine Modulation of Metabolic Effects in Overweight Adolescents

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00140842
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Duration (Months): 25
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 47 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Neuroendocrine Modulation of Metabolic Effects in Overweight Adolescents
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Jun 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Obese girls The inclusion criteria will be girls 12-18 years of age. According to the Centers for Disease Control and Prevention, the definition of obesity is a BMI higher than the 95th percentile for age and sex, and that of overweight is a BMI between the 85th and 95th percentiles. Cases will be defined as having a body mass index (BMI) greater than the 95th percentile for age according to the 2000 Centers for Disease Control and Prevention growth charts.
Normal-weight girls

Outcome Measures

Primary Outcome Measures

1. Peak Growth Hormone (GH) on the GH Stimulation Test [Baseline]

   Peak growth hormone (GH) on the GH stimulation test is a measure of the adequacy of GH secretion.

Secondary Outcome Measures

1. Visceral Adipose Tissue [Baseline]

   Visceral adipose tissue was measured using magnetic resonance imaging at the level of the fourth lumbar vertebra (L4)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 18 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Madhusmita Misra, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information about this study: Neuroendocrine Modulation of Metabolic Effects in Overweight Adolescents

Publications

None provided.

• Responsible Party: Madhusmita Misra, Chief, Pediatric Endocrinology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00140842
• Other Study ID Numbers: 2004-P-002191
• First Posted: Sep 1, 2005
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Madhusmita Misra, Chief, Pediatric Endocrinology, Massachusetts General Hospital: Obesity, adolescent, ghrelin, growth hormone, cortisol
• Additional relevant MeSH terms: Overweight

Study Results

Participant Flow

Recruitment Details	17 obese and 30 normal-weight adolescents (12-18 yr old) were screened for study eligibility.15 obese adolescents completed the study visit. These subjects were matched for race, ethnicity, and bone age to normal-weight adolescents from the pool of screened subjects.

Arm/Group Title	Normal-weight Girls	Obese Girls
Arm/Group Description	Normal weight girls 12-18 years old	Obese adolescents between 12-18 years old.
Period Title: Overall Study
STARTED	15	15
COMPLETED	15	15
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Normal-weight Girls	Obese Girls	Total
Arm/Group Description	Normal-weight girls were required to have a BMI between the 15th-85th percentiles	Obese girls were required to have a BMI above the 95th percentile	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	15 100%	15 100%	30 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.9 (1.7)	14.0 (1.9)	14.9 (3.3)
Sex: Female, Male (Count of Participants)
Female	15 100%	15 100%	30 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Peak Growth Hormone (GH) on the GH Stimulation Test
Description	Peak growth hormone (GH) on the GH stimulation test is a measure of the adequacy of GH secretion.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

This was a cross-sectional study to compare differences in growth hormone (GH) secretory status in relation to body composition in obese versus normal-weight girls. This was a pilot study and the analysis was performed using a Student t-test to compare means across groups

Arm/Group Title	Normal-weight Girls	Obese Girls
Arm/Group Description	Normal-weight girls were required to have a BMI between the 15th-85th percentiles	Obese girls were required to have a BMI above the 95th percentile
Measure Participants	15	15
Mean (Standard Deviation) [ng/ml]	40.1 (16.1)	25.2 (21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal-weight Girls, Obese Girls
	Comments	The null hypothesis was that there is no difference between the groups for peak growth hormone on the growth hormone stimulation test.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 16
	Estimation Comments

2. Secondary Outcome

Title	Visceral Adipose Tissue
Description	Visceral adipose tissue was measured using magnetic resonance imaging at the level of the fourth lumbar vertebra (L4)
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The analysis was completed on the 30 participants as per protocol

Arm/Group Title	Normal-weight Girls	Obese Girls
Arm/Group Description	Normal-weight girls were required to have a BMI between the 15th-85th percentiles	Obese girls were required to have a BMI above the 95th percentile
Measure Participants	15	15
Mean (Standard Deviation) [grams]	19 (7.5)	42.7 (17.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal-weight Girls, Obese Girls
	Comments	The null hypothesis is that there is no difference between the groups for visceral adipose tissue
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	23.7
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 12
	Estimation Comments

Adverse Events

Arm/Group Title	Normal-weight Girls		Obese Girls
Arm/Group Description	Normal-weight girls were required to have a BMI between the 15th-85th percentiles		Obese girls were required to have a BMI above the 95th percentile
All Cause Mortality
	Normal-weight Girls		Obese Girls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Normal-weight Girls		Obese Girls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Normal-weight Girls		Obese Girls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)

Limitations/Caveats

Limited number of participants-pilot study

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.