Growth Hormone as a Determinant of Weight Regulation

NCT00355784 | Completed Results

• 2 other identifiers: R01DK071955-01R01DK071955
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

With the alarming increase in the prevalence of obesity, identifying factors that predispose individuals to weight-gain is of critical importance. Even when caloric intake and physical activity levels are well controlled, susceptibility for weight-gain is heterogeneous. Basal metabolic rate (BMR) represents the largest portion of daily energy expenditure in normal adults, and as such, variability in BMR among individuals can be a major factor in determining the susceptibility for gaining weight. However, factors responsible for this variability in BMR and resistance to weight-gain remain unclear. Our preliminary data indicate that high-normal growth hormone (GH) concentration is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. In addition, the investigators have found that the pulsatility of GH secretion has profound effects on several metabolic processes. Therefore, together these findings suggest that endogenous GH secretion is associated with body weight regulation, and the pulsatility (peak amplitude) of GH secretion, rather than the absolute GH concentration, per se, may be responsible for this effect. Because GH influences many of the key metabolic processes that contribute to BMR (e.g.; protein synthesis, proteolysis, substrate cycling), the investigators anticipate that the resistance to weight-gain in persons with elevated GH concentrations will be associated with an increase in BMR due to acceleration of some or all of these processes. Our overall hypothesis is that increased GH secretion can protect against weight-gain due to an augmentation of major metabolic processes that contribute to BMR. Identifying factors responsible for predisposing individuals to weight-gain will lead to establishing improved methods for reducing the prevalence of obesity.

Conditions

Obesity

Keywords

growth hormone; overfeeding; energy expenditure; protein metabolism; lipid metabolism

Outcome Measures

Primary Outcomes (9)

• 24 Hour Average Plasma Growth Hormone Concentration

  2 weeks

• Changes in Body Weight

  2 weeks

• Baseline Whole Body Protein Turnover

  Whole body proteolytic rate (Leucine Ra)

  baseline

• Baseline Skeletal Muscle Protein Synthesis

  after an overnight fast

  baseline

• Lipolytic Rate

  2 weeks

• Whole Body Protein Turnover After 2 Week Intervention

  whole body proteolytic rate (leucine Ra)

  2 weeks

• 2 Week Skeletal Muscle Protein Synthesis

  after an overnight fast

  2 weeks

• Changes in Fat Mass

  2 weeks

• Changes in Fat-free Mass

  2 weeks

Study Arms (3)

Control

OTHER

9 non-obese (initial body mass index 23.5 +/- 0.3 kg/m2), weight stable, relatively sedentary (physical activity \</- 2h/week), healthy adults not taking any medications were admitted to the hospital for 2 weeks during which time they ate \~4000 kcal/day and their plasma growth hormone concentration was allowed to decline naturally.

Other: overfeeding

Growth Hormone Treatment

EXPERIMENTAL

8 non-obese (initial body mass index 23.5 +/- 0.3 kg/m2), weight stable, relatively sedentary (physical activity \</- 2h/week), healthy adults not taking any medications were admitted to the hospital for 2 weeks during which time they ate \~4000 kcal/day and received exogenous growth hormone treatment administered in 4 daily injections to mimic physiological growth hormone secretion throughout the 2-week overeating period.

Other: overfeeding; Drug: growth hormone treatment

High Growth Hormone Treatment

EXPERIMENTAL

5 non-obese (initial body mass index 23.5 +/- 0.3 kg/m2), weight stable, relatively sedentary (physical activity \</- 2h/week), healthy adults not taking any medications were admitted to the hospital for 2 weeks during which time they ate \~4000 kcal/day and received a relatively high daily dose of growth hormone.

Other: overfeeding; Drug: growth hormone treatment

Interventions

overfeeding OTHER

overfeeding 2000kcals/day above energy requirements for 14d

Control; Growth Hormone Treatment; High Growth Hormone Treatment

growth hormone treatment DRUG

growth hormone administrated for 2 weeks (dose = 1.0 mg/m2/d)

Growth Hormone Treatment; High Growth Hormone Treatment

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age = 21-35 years Weight stable (\< ± 5 pound over past 6 months) Premenopausal (women only) Body mass index 18 - 26 kg/m2 Must be willing to be randomized to receive GH infusion during 2 week Michigan Clinical Research Unit (MCRU) visit

You may not qualify if:

• Evidence of metabolic or cardiovascular disease Pregnancy (women only) Hyperlipidemia (fasting plasma triglyceride concentration \> 150 mg/dl) Hematocrit \< 34% Liver Function test abnormalities participating in a regular exercise program (\> 2 h/week) taking any prescription medication (except birth control)

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The short duration of our intervention was a limitation. The metabolic measurements that were performed in the postabsorptive state was a limitation.

Results Point of Contact

• Title: Jeffrey F. Horowitz
• Organization: University of Michigan, Ann Arbor, Michigan

jeffhoro@umich.edu

734-647-1076

Study Officials

• Jeffrey F. Horowitz, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Movement Science, School of Kinesiology

Study Record Dates

• First Submitted: July 24, 2006
• First Posted: July 25, 2006
• Study Start: September 1, 2005
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2015
• Last Updated: January 1, 2016
• Results First Posted: July 22, 2013

Record last verified: 2015-12

Locations

US (1)