The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin

Study Overview
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Brief Summary
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This study will investigate the non-growth-hormone-dependent metabolic effects of the hormone Ghrelin in growth hormone deficient subjects by examining the insulin tolerance as well as signal proteins in fat and muscle biopsies.

Detailed Description
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Ghrelin is a relatively 'new' hormone that is produced in the stomach and to a lesser extend in the hypothalamus of the brain. The actions of ghrelin are diverse and includes stimulation of the appetite center of the brain and the release of growth hormone. We have for the first time shown that ghrelin also stimulates the metabolism of fatty acids and induces insulin resistance in skeletal muscle. These effects have we confirmed in growth hormone deficient subjects on a stabile substitution treatment with growth hormone and hydrocortisone. With these subjects we can investigate the effects of ghrelin that are independent of growth hormone. The present study is a continuation of these findings, as we wish to investigate whether the insulin resistance effect of ghrelin is dependent of the concomitant metabolism of fatty acids. This is possible by administration of the niacin acid antagonist Acipimox, that blocks the fatty acid metabolism reversibly. We have applied this experimental principle in other settings with success. Knowledge of the effects of ghrelin in general 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.

Official Title
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The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin

Conditions
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Metabolism, Insulin Resistance, Hypopituitarism

Intervention / Treatment
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* Drug: Acipimox
* Drug: Ghrelin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males with hypopituitarism in regard to growth hormone and ACTH in stabile treatment regime age 18-65 BMI 20-35 Exclusion Criteria: abuse of alcohol malign disease medication other than that expected for hypopituitarism known disease other than hypopituitarism participation in isotope investigations the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ghrelin / Acipimox<br>Ghrelin infusion and tablet acipimox | Drug: Acipimox<br>* Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day<br>* Other names: Tablet Olbetam 250 mg;Drug: Ghrelin<br>* Ghrelin infusion 4.2 ng/kg/min throughout the investigation day<br>|
| Active Comparator: Ghrelin / placebo<br>Ghrelin infusion and placebo tablets | Drug: Ghrelin<br>* Ghrelin infusion 4.2 ng/kg/min throughout the investigation day<br>Other: Placebo<br>* placebo tablets or saline infusion<br>* Other names: Saline infusion;|
| Active Comparator: Placebo / Acipimox<br>saline infusion and tablet Acipimox | Drug: Acipimox<br>* Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day<br>* Other names: Tablet Olbetam 250 mg;Other: Placebo<br>* placebo tablets or saline infusion<br>* Other names: Saline infusion;|
| Placebo Comparator: Placebo / placebo<br>saline infusion and placebo tablets | Other: Placebo<br>* placebo tablets or saline infusion<br>* Other names: Saline infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ghrelin during basal and hyperinsulinemic conditions | Growth hormone deficient patient investigated with ghrelin infusion and pharmacological antilipolysis (Acipimox) in a randomized cross-over study with 4 study days. During each visit signal proteins in muscle and fat biopsies are investigated with PCR, wester blot and activity assays for ghrelin, growth hormone and insulin. Further is glucose metabolism investigated in basal conditions and during hyperinsulinemic euglycemic clamp. | 5 hours investigation day | 
| Effects of ghrelin during basal and hyperinsulinemic conditions | Effects of ghrelin on heart rate variability | 5 hours investigation day | 
| Effects of ghrelin during basal and hyperinsulinemic conditions | Effects of ghrelin on thirst, fluid intake, urine production and natriuresis | 5 hours investigation day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ghrelin, metabolism, type 2 diabetes, insulin resistance