The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin

Sponsor

University of Aarhus (Other)

Overall Status

Completed

CT.gov ID

NCT01209416

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolism Insulin Resistance Hypopituitarism	Drug: Acipimox Drug: Ghrelin Other: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Basic Science

Official Title:

The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ghrelin / Acipimox Ghrelin infusion and tablet acipimox	Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Names: Tablet Olbetam 250 mg Drug: Ghrelin Ghrelin infusion 4.2 ng/kg/min throughout the investigation day
Active Comparator: Ghrelin / placebo Ghrelin infusion and placebo tablets	Drug: Ghrelin Ghrelin infusion 4.2 ng/kg/min throughout the investigation day Other: Placebo placebo tablets or saline infusion Other Names: Placebo tablets Saline infusion
Active Comparator: Placebo / Acipimox saline infusion and tablet Acipimox	Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Names: Tablet Olbetam 250 mg Other: Placebo placebo tablets or saline infusion Other Names: Placebo tablets Saline infusion
Placebo Comparator: Placebo / placebo saline infusion and placebo tablets	Other: Placebo placebo tablets or saline infusion Other Names: Placebo tablets Saline infusion

Outcome Measures

Primary Outcome Measures

Effects of ghrelin during basal and hyperinsulinemic conditions [5 hours investigation day]
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.
Effects of ghrelin during basal and hyperinsulinemic conditions [5 hours investigation day]
Effects of ghrelin on heart rate variability
Effects of ghrelin during basal and hyperinsulinemic conditions [5 hours investigation day]
Effects of ghrelin on thirst, fluid intake, urine production and natriuresis