The Relationship Between Body Composition and Growth Hormone, SIRT Signaling, Protein Turnover and Insulin Sensitivity

This study is currently recruiting participants.

Verified June 2012 by University of Aarhus

Sponsor:

Collaborator:

Aarhus University Hospital

Information provided by (Responsible Party):

University of Aarhus

ClinicalTrials.gov Identifier:

NCT01299831

First received: January 21, 2011

Last updated: June 25, 2012

Last verified: June 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	January 21, 2011
Last Updated Date	June 25, 2012
Start Date ^ICMJE	January 2011
Estimated Primary Completion Date	December 2013 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: February 17, 2011)	Measurements of changes in metabolism [ Time Frame: 6 hours ] [ Designated as safety issue: No ] Measurements of the switch to lipid metabolism during fasting in lean and obese human subjects.
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01299831 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: February 17, 2011)	Signaling pathways in muscle and fat tissue involved in regulation of metabolism [ Time Frame: 6 hours ] [ Designated as safety issue: No ] Protein and gene-exspression, phosphorylation and acetylation of specific proteins involved in lipid-, glucose and protein metabolism.
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	The Relationship Between Body Composition and Growth Hormone, SIRT Signaling, Protein Turnover and Insulin Sensitivity
Official Title ^ICMJE	THE RELATIONSHIP BETWEEN BODY COMPOSITION AND GROWTH HORMONE, SIRT SIGNALING, PROTEIN TURNOVER AND INSULIN SENSITIVITY. Studies of Signaling Pathways in Fat and Muscle, and Turnover of Protein, Sugar and Fat After Stimulation With Growth Hormone and During Fasting in Lean and Obese Subjects
Brief Summary	The purpose of this study is to investigate signaling pathways in fat and muscle, as well as turnover of protein, sugar and fat after stimulation with growth hormone and during fasting in lean and obese subjects. This will help clarify differences in the human metabolism between lean and obese subject and provide us with a better understanding of the molecular mechanisms regulating the basic metabolism during prolonged fasting.
Detailed Description	In an evolutionary context, it is likely that "inherited" obesity provides a survival advantage when there are shortages of food, but also increases the risk of lifestyle diseases in times of prosperity. This may explain the high incidence of obesity, diabetes and cardiovascular disease in the western world today. Obese individuals have high levels of free fatty acids (FFAs) in the blood and FFAs are both protein sparing (giving an evolutionary survival advantage) but also cause increased insulin resistance (which increases the risk of diabetes and cardiovascular disease). Obesity also leads to low growth hormone (GH)-levels, whereas fasting is accompanied by high GH- and FFA-levels and increased IGF-I mRNA in muscle. It is likely that obese individuals are more capable of fasting than lean individuals and will lose less protein during fasting, have increased activation of GH signaling and altered activation of other signaling proteins. And obese individuals are likely to be more sensitive to growth hormone than lean individuals based on FFA-responses, intracellular signaling, protein loss and insulin sensitivity. We would like to test 3 hypotheses: (1) Obese individuals are more capable of fasting than lean individuals and will lose less protein during fasting (2) Activation of lipolysis is an important prerequisite for limiting protein loss during fasting in both slim as obese individuals. (3) Obese individuals are more sensitive to growth hormone than lean individuals based on FFA responses and activation of intracellular signals. The hypotheses are tested in 8 lean and 8 obese healthy young men, who are studied 4 times: (i) after 12 hours of fasting (ii) after 72 hours of fasting (iii) after GH-bolus (0.005 mg/kg over 20 min.) and (iv) after 72 hours of fasting with inhibition of fat metabolism (tablet acipimox 250 mg every 4 hours) during the last 12 hours of fasting and during the study period. Each study period consists of a 4-hour basal period and a 2 hour hyperinsulinemic euglycemic clamp (30 mU/m2/min). Muscle- and fat-biopsies are taken and analyzed for enzyme expression and activation of various signaling pathways. The study subjects are given glucose-, amino acid-, urea- and palmitate-tracers and specific hormones and metabolites are measured for assessment of underlying molecular mechanisms regulating the basic human energy metabolism.
Study Type ^ICMJE	Interventional
Study Phase	Not Provided
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
Condition ^ICMJE	Healthy
Intervention ^ICMJE	Behavioral: 72 hour fast The participants will be fasting 72 hours prior to the start of the study day, drinking water is allowed. Behavioral: control, 12 hour fast The 12 hour fast will be used as a basic metabolic control Drug: Growth hormone Genotropin bolus(0,005 mg/kg over 20 min.) will be administered at the beginning of the study day after a 12 hour fast. Drug: Olbetam The participants will be fasting 72 hours prior to the start of the study day, drinking water is allowed. During the last 12 hours of fasting and the study day lipolysis will be inhibited with one tablet of olbetam 250 mg every 4 hours.
Study Arm (s)	No Intervention: 72 hour fast Intervention: Behavioral: 72 hour fast No Intervention: 12 hours fast Intervention: Behavioral: control, 12 hour fast Experimental: 12 hour fast, growth hormone bolus Intervention: Drug: Growth hormone Experimental: 72 hour fast, inhibition of lipolysis Intervention: Drug: Olbetam
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Recruiting
Estimated Enrollment ^ICMJE	16
Estimated Completion Date	December 2013
Estimated Primary Completion Date	December 2013 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: healthy lean (BMI19-25) and healthy obese (BMI 32-40) men written consent before study start Exclusion Criteria: known medical conditions any medication
Gender	Male
Ages	20 Years to 35 Years
Accepts Healthy Volunteers	Yes
Contacts ^ICMJE	Not Provided
Location Countries ^ICMJE	Denmark

Administrative Information
NCT Number ^ICMJE	NCT01299831
Other Study ID Numbers ^ICMJE	M-2010082
Has Data Monitoring Committee	No
Responsible Party	University of Aarhus
Study Sponsor ^ICMJE	University of Aarhus
Collaborators ^ICMJE	Aarhus University Hospital
Investigators ^ICMJE	Not Provided
Information Provided By	University of Aarhus
Verification Date	June 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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