Clinical trial NCT01209416: The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
Official title: The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolism
Insulin Resistance
Hypopituitarism
Keywords: ghrelin
metabolism
type 2 diabetes
insulin resistance
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2010-09-27
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effects of ghrelin during basal and hyperinsulinemic conditions
timeFrame: 5 hours investigation day
measure: Effects of ghrelin during basal and hyperinsulinemic conditions
timeFrame: 5 hours investigation day
measure: Effects of ghrelin during basal and hyperinsulinemic conditions
timeFrame: 5 hours investigation day
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: University Hospital of Aarhus
Study officials:
affiliation: University Hospital of Aarhus
name: Jens Otto L Jørgensen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jepsen SL, Vestergaard ET, Larraufie P, Gribble FM, Reimann F, Jorgensen JOL, Holst JJ, Kuhre RE. Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1. J Clin Endocrinol Metab. 2020 Jan 1;105(1):266-75. doi: 10.1210/clinem/dgz046.
citation: Vestergaard ET, Cichosz SL, Moller N, Jorgensen JOL, Fleischer J. Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation. Br J Clin Pharmacol. 2017 Dec;83(12):2671-2677. doi: 10.1111/bcp.13384. Epub 2017 Aug 24.