Clinical trial NCT02500095: Substrate Metabolism, Growth Hormone Signaling, and Insulin Sensitivity During Fasting
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2015-07-16
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: Inclusion Criteria:

* healthy men
* written consent
* body mass index (BMI) 25-40
* age 20-60 years

Exclusion Criteria:

* any kind of disease
* regular medication

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.
timeFrame: 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
timeFrame: 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)
measure: Magnetic resonance (MR) spectroscopy
timeFrame: During fasting: t= 12 hours and t= 48 hours of fasting
measure: Change in concentrations of metabolites in the insulin and growth hormone signaling pathways using metabolomics
timeFrame: 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)
measure: Fat metabolism
timeFrame: 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)
measure: Protein metabolism
timeFrame: 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)
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University / Aarhus University Hospital
name: Jens Otto L. Jørgensen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University / Aarhus University Hospital
name: Jens Otto L. Jørgensen, Professor
role: STUDY_CHAIR
References:
citation: Hogild ML, Gudiksen A, Pilegaard H, Stodkilde-Jorgensen H, Pedersen SB, Moller N, Jorgensen JOL, Jessen N. Redundancy in regulation of lipid accumulation in skeletal muscle during prolonged fasting in obese men. Physiol Rep. 2019 Nov;7(21):e14285. doi: 10.14814/phy2.14285.