Lipolytic Effects of GH in Hypopituitary Patients in Vivo
- Conditions
- HypopituitarismInsulin ResistanceEndocrine System DiseasesGlucose Metabolism DisordersMetabolic DiseasesPituitary DiseasesBrain Diseases
- Interventions
- Registration Number
- NCT02782208
- Lead Sponsor
- University of Aarhus
- Brief Summary
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism.
GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH.
The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism.
In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed.
Knowledge of the effects of growth hormone and fat metabolism can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 9
- hypopituitary patients with documented GH-deficiency
- other significant disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Acipimox/GH pause GH pause Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day. Acipimox/GH substitution GH substitution Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually. Placebo/GH substitution Placebo Drug: Placebo tablets Continue GH substitution as usually. Placebo/GH substitution GH substitution Drug: Placebo tablets Continue GH substitution as usually. Placebo/GH pause Placebo Drug: Placebo tablets Pause GH substitution to days prior to the study day. Placebo/GH pause GH pause Drug: Placebo tablets Pause GH substitution to days prior to the study day. Acipimox/GH substitution Acipimox Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually. Acipimox/GH pause Acipimox Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day.
- Primary Outcome Measures
Name Time Method Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions. 1 year
- Secondary Outcome Measures
Name Time Method Insulin sensitivity as measured by M value and GIR (glucose infusion rate) 6 months GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR 1,5 years Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites 1 year PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay 1 year
Trial Locations
- Locations (1)
University Hospital of Aarhus
🇩🇰Aarhus, Denmark