Clinical trial NCT01762540: Glucocorticoid Induced Whole Body Catabolisme
Official title: Glucocorticoid Induced Inhibition of IGF-I Activity: Exploring Underlying Mechanisms.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Whole Body Catabolisme Induced by Glucocorticoids
Keywords: Protein breakdown
Insulin resistance
Glucose intolerance
Lipolysis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: The Ministry of Science, Technology and Innovation, Denmark
First posted: 2013-01-07
Enrollment: 19
Sex: MALE
Minimum age (years): 20
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of the trial is to advance our knowledge on the possible mechanism underlying the catabolic effects of long-term treatment with glucocorticoid.

Detailed description: Long-term treatment with glucocorticoid induces a general state of catabolism and increases insulin resistance. The underlying mechanisms are insufficiently characterized, however glucocorticoid induced changes of Growth Hormone (GH) and the Insulin-like growth factor I (IGF-I) appear to be of outmost importance.

We wish to investigate the mechanism behind glucocorticoid induced catabolism and insulin resistance.

More specific we wish to investigate:

* Whether glucocorticoid induces IGF-I inhibiting substances in serum or interstitial fluid that block the ability of IGF-I to phosphorylate its receptor in vitro
* Whether glucocorticoid inhibits intracellular IGF-I and insulin signaling in vitro and in vivo
* The mechanisms by which growth hormone counteracts the CG-mediated inhibition of IGF-I action

Eligibility criteria: Inclusion Criteria:

* signed and dated informed consent
* healthy subjects
* sex: male
* age 20-30 years
* BMI 19-26 kg/m2
* normal HbA1c

Exclusion Criteria:

* suspected og known allergy to the trial drug or similar medications.
* known current illness including diabetes mellitus, ischemic heart disease or cardiac arrhythmia.
* Daily drug intake (excluding Over-the-Counter medicines).
* Known or previous mental illness
* Current participation or previous participation in experiments using ionizing radiation for a year prior to inclusion in this study.
* Participation in a larger X-ray examinations in trial period.

Primary outcomes:
measure: Insulin-like Growth Factor (IGF)-I profiles of subjects before and after prednisolone-treatment.
timeFrame: day 1, 3 and 5
Secondary outcomes:
measure: Intracellular signaling of IGF-I under the influence/abscence of prednisolone.
timeFrame: day 5
measure: Insulin sensitivity under the influence/abscence of prednisolone.
timeFrame: Day 5
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Medical Research Laboratory, Clinical Institute of Medicine, Aarhus University Hospital
Study officials:
affiliation: Medical Research Laboratory, Clinical institute of Medicine, Aarhus University Hospital
name: Jan Frystyk, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramshanker N, Jessen N, Voss TS, Pedersen SB, Jorgensen JOL, Nielsen TS, Frystyk J, Moller N. Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans. Metabolism. 2019 Oct;99:1-10. doi: 10.1016/j.metabol.2019.06.013. Epub 2019 Jun 29.
citation: Ramshanker N, Aagaard M, Hjortebjerg R, Voss TS, Moller N, Jorgensen JOL, Jessen N, Bjerring P, Magnusson NE, Bjerre M, Oxvig C, Frystyk J. Effects of Prednisolone on Serum and Tissue Fluid IGF-I Receptor Activation and Post-Receptor Signaling in Humans. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4031-4040. doi: 10.1210/jc.2017-00696.