- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00355784
Growth Hormone as a Determinant of Weight Regulation
December 2, 2015 updated by: Jeffrey F Horowitz, University of Michigan
Growth Hormone as a Determinant of Weight Regulation.
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
The susceptibility to gain weight is highly variable even when caloric intake and physical activity are well controlled.
Because basal metabolic rate (BMR) represents ~70% of total daily energy expenditure (TDEE), even a small difference in BMR can affect daily energy balance, thereby increasing the susceptibility for gaining weight.
Our preliminary data indicate that high-normal growth hormone (GH) secretion is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed.
Given that GH influences many of the key metabolic processes that contribute to BMR, the investigators hypothesize that persons with high-normal GH will be resistant to weight-gain because of a high BMR, resulting from accelerated rates of these processes.
The investigators will measure basal 24h GH secretion and BMR in 106 non-obese men and women.
The investigators will also measure protein synthesis, proteolysis, triglyceride/fatty acid cycling (all measured using stable isotope tracer methods) to determine the relationships among these processes, BMR, and GH [Specific Aim 1].
Subjects identified as having "low-normal" (<1.5 ug/L) and "high-normal" (>3 ug/L) 24h GH will then be admitted to the hospital for a 2 wk overfeeding protocol (~2000 kcal/d >TDEE - with restricted physical activity), immediately followed by a 4 wk caloric restriction protocol (~750 kcal/d <TDEE) to compare changes in weight, body composition and intra-abdominal adiposity between these groups that differ markedly in their GH secretion (GH measured before the diet) [Specific Aim 2].
A subset of subjects with low-normal GH will receive intravenous GH throughout the 2 wk overfeeding period at either: 1. a constant rate or 2. as a pulsatile infusion (to mimic endogenous secretion).
BMR will be assessed daily and protein synthesis, proteolysis, and triglyceride/fatty acid cycling will be measured at the end of the 2 wks [Specific Aim 3].
The investigators anticipate that a higher GH pulsatility (peak amplitude), rather than elevated GH concentration, per se, will increase protein synthesis, proteolysis, and triglyceride/fatty acid cycling with a resultant increase in BMR and resistance to weight-gain.
Identifying factors responsible for predisposing individuals to weight-gain will help combat the alarming rise in the prevalence of obesity.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 35 years (ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
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
Exclusion Criteria:
- 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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Control
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.
|
overfeeding 2000kcals/day above energy requirements for 14d
|
EXPERIMENTAL: Growth Hormone Treatment
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.
|
overfeeding 2000kcals/day above energy requirements for 14d
growth hormone administrated for 2 weeks (dose = 1.0 mg/m2/d)
|
EXPERIMENTAL: High Growth Hormone Treatment
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.
|
overfeeding 2000kcals/day above energy requirements for 14d
growth hormone administrated for 2 weeks (dose = 1.0 mg/m2/d)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24 Hour Average Plasma Growth Hormone Concentration
Time Frame: 2 weeks
|
2 weeks
|
|
Changes in Body Weight
Time Frame: 2 weeks
|
2 weeks
|
|
Baseline Whole Body Protein Turnover
Time Frame: baseline
|
Whole body proteolytic rate (Leucine Ra)
|
baseline
|
Baseline Skeletal Muscle Protein Synthesis
Time Frame: baseline
|
after an overnight fast
|
baseline
|
Lipolytic Rate
Time Frame: 2 weeks
|
2 weeks
|
|
Whole Body Protein Turnover After 2 Week Intervention
Time Frame: 2 weeks
|
whole body proteolytic rate (leucine Ra)
|
2 weeks
|
2 Week Skeletal Muscle Protein Synthesis
Time Frame: 2 weeks
|
after an overnight fast
|
2 weeks
|
Changes in Fat Mass
Time Frame: 2 weeks
|
2 weeks
|
|
Changes in Fat-free Mass
Time Frame: 2 weeks
|
2 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Jeffrey F. Horowitz, PhD, University of Michigan
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2005
Primary Completion (ACTUAL)
December 1, 2011
Study Completion (ACTUAL)
December 1, 2015
Study Registration Dates
First Submitted
July 24, 2006
First Submitted That Met QC Criteria
July 24, 2006
First Posted (ESTIMATE)
July 25, 2006
Study Record Updates
Last Update Posted (ESTIMATE)
January 1, 2016
Last Update Submitted That Met QC Criteria
December 2, 2015
Last Verified
December 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R01DK071955-01 (NIH)
- R01DK071955 (NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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