Importance of the GH/IGF-1 Axis for Human Substrate and Energy Metabolism During Calorie Restriction

Study Overview
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Brief Summary
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This study will investigate whether growth hormone is modulated by the enzyme SIRT1 and by that is stimulating lipolysis on expense of IGF-I production. This is done in 10 healthy men on calorie restriction on 4 study days with fat and skeletal muscle biopsies.

Detailed Description
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It has been shown that calorie restriction enhances the length of life in yeast, worms, fish and rodent. Whether this elongation of life due to calorie restriction can be applied to humans is not known. However, it is a fact that calorie restriction will decrease the risk of developing metabolic disturbances such as diabetes, hypertension and atherosclerosis. On the molecular level the specific relations are not fully understood. This study will investigate the possible connection between SITR1 and the relation to the GH/IGF-I axis and STAT5b in healthy men. The participant will fast 42 and 12 hours respectively, and have GH or placebo infusions. The design is a classical 2x2 design and will be randomized. Knowledge of the interactions between calorie restriction, SIRT1, STAT5b and the GH/IGF-I axis will apply important information about the relations between aging, energy metabolism and metabolic disturbances.

Official Title
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Importance of the GH/IGF-1 Axis for Human Substrate and Energy Metabolism During Calorie Restriction

Conditions
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Healthy

Intervention / Treatment
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* Drug: GH hormone infusion
* Behavioral: 42 hour fast
* Behavioral: 12 hour fast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy lean men age >18 Exclusion Criteria: metabolic disturbances alcohol drug abuse malign disease: current or previous

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 42 hour fast/GH infusion<br> | Drug: GH hormone infusion<br>* Norditropin 30 ng/kg/min<br>* Other names: Genotropin;Behavioral: 42 hour fast<br>* The participant will be fasting 42 hours prior to the start of the study day, drinking water is allowed<br>* Other names: No other name;|
| Experimental: 42 hour fast/Placebo infusion<br> | Behavioral: 42 hour fast<br>* The participant will be fasting 42 hours prior to the start of the study day, drinking water is allowed<br>* Other names: No other name;|
| Experimental: 12 hour fast/GH infusion<br> | Drug: GH hormone infusion<br>* Norditropin 30 ng/kg/min<br>* Other names: Genotropin;Behavioral: 12 hour fast<br>* 12 hour fast will be used as a control scenario to 42 hour fast<br>* Other names: No other name;|
| Placebo Comparator: 12 hour fast/Placebo infusion<br> | Behavioral: 12 hour fast<br>* 12 hour fast will be used as a control scenario to 42 hour fast<br>* Other names: No other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of intracellular pathways to clarify the interplay between calorie restriction, SIRT1, STATb5, and the GH/IGF-I axis | All study days consists of 3 hour basic periods and 3 hours hyperinsulinemic, euglycemic clamp. | 6 hour study days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Calorie restriction, GH/IGF-I axis, STATb5, SIRT1, Intracellular signaling peptides and proteins, Fasting, Growth hormone, IGF-1