Clinical trial NCT00491582: The Effects of Growth Hormone (GH) on Lipid Depots
Official title: The Effect of Growth Hormone (GH) on Intramyocellular Lipids (IMCL), Intrahepatocellular Lipids (IHCL) and Visceral Fat Mass in Relation to Insulin Resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Growth Hormone Deficiency
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2007-06-26
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims at investigating the effect of growth hormone on lipid-content of muscle and liver as well as visceral fat mass in relation to insulin sensitivity.

In addition, hormonal regulation and free fatty availability is assessed during a physical exercise at 50-60% VO2max.

Finally, the value of physical exercise in diagnosing growth hormone deficiency is investigated.

Hypothesis: 1) Lipid content of muscle and liver change with physical exercise and exercise capacity and free fatty availability will influence these changes. 2)Growth hormone replacement therapy will predominantly reduce visceral fat mass and increase free fatty availability.

3)Free fatty availability during exercise will be reduced in growth hormone deficient patients 4)Physical exercise may be an alternative way to diagnose growth hormone deficiency

Detailed description: Using the two-step hyperinsulinaemic-euglycaemic clamp technique hepatic and peripheral insulin sensitivity is assessed.

Lipid depots (skeletal muscle and liver) are measured by MR-spectroscopy, visceral fat mass by MR-imaging.

Exercise capacity ist measured on a treadmill. Counterregulatory hormones, glucose and free fatty acids are measured during a 2h physical exercise at 50-60 VO2max Identical investigations are performed in adult growth hormone (GH) deficient patients before and after six months GH replacement therapy, in sedentary matched control subjects and in endurance trained athletes.

Eligibility criteria: Inclusion Criteria:

* Male and female patients with proven GH-deficiency defined as a peak GH of less than 3mU/l during an insulin provocation test with nadir plasma glucose less than 2.2 mmol/l and additionally, stable conventional replacement therapy including corticoids, thyroxin and gonadal hormones as needed.
* Ability to perform an exercise test on a treadmill or a walking band.
* Willingness to participate in the study and to give written informed consent.

Exclusion Criteria:

Active neoplasia

* Severe cardiovascular disease (unstable coronary heart disease, heart failure NYHA III-IV)
* Type 2 Diabetes mellitus
* Haemophilia or other coagulation disorder
* Inability to exercise
* Contraindications to exposure to a 3-T magnetic field (Pace-Makers, osteosynthetic material)
* Pregnant women
* Women in childbearing age unless on a continuous contraceptive therapy or surgically sterilised.
* Abnormal liver or renal function (Creatinine \>130mmol/L, normal reference 45-93mmol/L; ASAT and ALAT \> 3 times the upper reference limit).
* Major depression, psychosis and other severe personality disorders
* Excessive alcohol consumption (\>60g/d) or drug-abuse
* Refusal to give written consent
* Patients, who are not suitable for the study according to the study physician

Primary outcomes:
measure: Determination of visceral fat mass by MRI,Determination of IMCL and IHCL by MR Spectroscopy, Determination of peripheral and hepatic insulin sensitivity by two step hyperinsulinemic euglycemic clamp
timeFrame: 2008 - 2009
Secondary outcomes:
measure: maximal exercise capacity
timeFrame: 2008 - 2009
measure: Measurement of serum alphaKlothe by an ELISA
timeFrame: 2008 - 2013
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Abt. für Endokrinologie, Diabetologie und Klin. Ernährung, Inselspital
Study officials:
affiliation: Abt. für Endokrinologie, Diabetologie und Klin. Ernährung, Inselspital, Berne
name: Emanuel R Christ, Prof,MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Egger A, Kreis R, Allemann S, Stettler C, Diem P, Buehler T, Boesch C, Christ ER. The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids in healthy subjects. PLoS One. 2013 Aug 14;8(8):e70865. doi: 10.1371/journal.pone.0070865. eCollection 2013.