Overview

This trial has been completed.

Condition healthy
Treatments fasting, saline, pegvisomant
Sponsor University of Aarhus
Start date July 2015
End date November 2016
Trial size 10 participants
Trial identifier NCT02500095, fasting8000

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking single blind (subject)
Primary purpose basic science
Arm
(No Intervention)
12 hours of fasting
(Experimental)
72 hours of fasting and concomitant saline
fasting
72 hours of fasting
saline
Concomitant saline during fasting
(Experimental)
72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion
fasting
72 hours of fasting
pegvisomant
Concomitant Growth hormone receptor blockade with Pegvisomant during fasting

Primary Outcomes

Measure
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.
time frame: 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)

Secondary Outcomes

Measure
Glucose metabolism
time frame: 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)
Magnetic resonance (MR) spectroscopy
time frame: During fasting: t= 12 hours and t= 48 hours of fasting
Change in concentrations of metabolites in the insulin and growth hormone signaling pathways using metabolomics
time frame: 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)
Fat metabolism
time frame: 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)
Protein metabolism
time frame: 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)

Eligibility Criteria

Male participants from 20 years up to 60 years old.

Inclusion Criteria: - healthy men - written consent - body mass index (BMI) 25-40 - age 20-60 years Exclusion Criteria: - any kind of disease - regular medication

Additional Information

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
Principal investigator Jens Otto L. Jørgensen, Professor
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University of Aarhus.