Substrate Metabolism, Growth Hormone Signaling, and Insulin Sensitivity During Fasting

Healthy Clinical Trial

Official title:

Substrate Metabolism, Growth Hormone Signaling, and Insulin Sensitivity During Fasting in Overweight and Obese Human Subjects and the Impact of Growth Hormone Receptor Blockade

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02500095
• Other study ID #: fasting8000
• Status: Completed
• Phase: N/A
• First received: July 10, 2015
• Last updated: November 22, 2016
• Start date: July 2015
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

Background: Calorie restriction increases longevity in many species and attenuate the development of chronic disorders including type 2 diabetes, cardiovascular diseases and cancer. In mice reduced activity of insulin-like growth factor I (IGF-I) and/or insulin is associated with extended longevity. Growth hormone (GH) is the main regulator of IGF-I production, but the molecular mechanism whereby GH switches from IGF-I stimulation (protein anabolism) to fatty acid oxidation (fatty acid catabolism) as well as induction of insulin resistance during fasting remains enigmatic.

Hypotheses: The changes of the global set of metabolites, induction of insulin resistance, and the shift in metabolism from protein anabolism to lipolysis together with the potentially favorable effect of calorie restriction during fasting depend on preserved fasting-induced GH secretion.

Aim: The investigators wish to provide knowledge on changes in metabolites and shift in signaling pathways that take place at the transition to the fasting state among healthy overweight and obese subjects. Furthermore the investigators wish to determine the effect of GH on the adaption of the metabolism to a fasting state.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

• healthy men

• written consent

• body mass index (BMI) 25-40

• age 20-60 years

Exclusion Criteria:

• any kind of disease

• regular medication

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy
• Insulin Resistance

Intervention

Other:
• Fasting
72 hours of fasting

Drug:
• Saline
Concomitant saline during fasting
• Pegvisomant
Concomitant Growth hormone receptor blockade with Pegvisomant during fasting

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin and growth hormone signaling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in messenger ribonucleic acid (mRNA) expression of target genes in muscle- and fat-tissue.	Change in phosphorylation of target proteins and mRNA expression of target genes	Muscle and fat biopsies obtained at t1= 9.00 am (60 min) and t2=12.30 am (270 min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)	No
Secondary	Glucose metabolism	Change in glucose metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.	Change in glucose metabolism using glucose tracer from t=0 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)	No
Secondary	Magnetic resonance (MR) spectroscopy		During fasting: t= 12 hours and t= 48 hours of fasting	No
Secondary	Change in concentrations of metabolites in the insulin and growth hormone signaling pathways using metabolomics	Method: Metabolomics	Muscle-tissue obtained at t1= 9.00 am (60 min) and t2=12.30 am (270min) on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)	No
Secondary	Fat metabolism	Change in fat metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.	Change in fat metabolism using palmitic acid tracer from t1=180 min - 240 min and t2=300 min - 360 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)	No
Secondary	Protein metabolism	Change in protein metabolism assessed by tracer kinetics on every study day and by indirect calorimetry.	Change in protein metabolism using urea tracer from t=0 min - 240 min on each study day after 0, 4 and 8 weeks (interval of 4 weeks between each of the three study days)	No