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

NCT02500095 | Completed DMC

• 1 other identifier: fasting8000
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Glucose metabolism

  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

  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

  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

  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

  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)

Study Arms (3)

Control

NO INTERVENTION

12 hours of fasting

Fasting and saline

EXPERIMENTAL

72 hours of fasting and concomitant saline

Other: Fasting; Drug: Saline

Fasting and GHR blockade

EXPERIMENTAL

72 hours of fasting and concomitant Growth hormone receptor (GHR) blockade with Pegvisomant (Somavert) for inhibition of the fasting-induced GH secretion

Other: Fasting; Drug: Pegvisomant

Interventions

Fasting OTHER

72 hours of fasting

Fasting and GHR blockade; Fasting and saline

Saline DRUG

Concomitant saline during fasting

Fasting and saline

Pegvisomant DRUG

Concomitant Growth hormone receptor blockade with Pegvisomant during fasting

Fasting and GHR blockade

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• any kind of disease
• regular medication

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Related Publications (1)

• 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.

  PMID: 31724339 DERIVED

MeSH Terms

Interventions

Angptl4 protein, mouse; Sodium Chloride; pegvisomant

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jens Otto L. Jørgensen, Professor

  Aarhus University / Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Jens Otto L. Jørgensen, Professor

  Aarhus University / Aarhus University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2015
• First Posted: July 16, 2015
• Study Start: July 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: November 23, 2016

Record last verified: 2016-11

Locations

DK (1)