The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
Primary Purpose
Metabolism, Insulin Resistance, Hypopituitarism
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Acipimox
Ghrelin
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Metabolism focused on measuring ghrelin, metabolism, type 2 diabetes, insulin resistance
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
Sites / Locations
- University Hospital of Aarhus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
Ghrelin / Acipimox
Ghrelin / placebo
Placebo / Acipimox
Placebo / placebo
Arm Description
Ghrelin infusion and tablet acipimox
Ghrelin infusion and placebo tablets
saline infusion and tablet Acipimox
saline infusion and placebo tablets
Outcomes
Primary Outcome Measures
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.
Effects of ghrelin during basal and hyperinsulinemic conditions
Effects of ghrelin on heart rate variability
Effects of ghrelin during basal and hyperinsulinemic conditions
Effects of ghrelin on thirst, fluid intake, urine production and natriuresis
Secondary Outcome Measures
Full Information
NCT ID
NCT01209416
First Posted
September 24, 2010
Last Updated
October 27, 2017
Sponsor
University of Aarhus
1. Study Identification
Unique Protocol Identification Number
NCT01209416
Brief Title
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
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
June 2012 (Actual)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolism, Insulin Resistance, Hypopituitarism
Keywords
ghrelin, metabolism, type 2 diabetes, insulin resistance
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ghrelin / Acipimox
Arm Type
Active Comparator
Arm Description
Ghrelin infusion and tablet acipimox
Arm Title
Ghrelin / placebo
Arm Type
Active Comparator
Arm Description
Ghrelin infusion and placebo tablets
Arm Title
Placebo / Acipimox
Arm Type
Active Comparator
Arm Description
saline infusion and tablet Acipimox
Arm Title
Placebo / placebo
Arm Type
Placebo Comparator
Arm Description
saline infusion and placebo tablets
Intervention Type
Drug
Intervention Name(s)
Acipimox
Other Intervention Name(s)
Tablet Olbetam 250 mg
Intervention Description
Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day
Intervention Type
Drug
Intervention Name(s)
Ghrelin
Intervention Description
Ghrelin infusion 4.2 ng/kg/min throughout the investigation day
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablets, Saline infusion
Intervention Description
placebo tablets or saline infusion
Primary Outcome Measure Information:
Title
Effects of ghrelin during basal and hyperinsulinemic conditions
Description
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.
Time Frame
5 hours investigation day
Title
Effects of ghrelin during basal and hyperinsulinemic conditions
Description
Effects of ghrelin on heart rate variability
Time Frame
5 hours investigation day
Title
Effects of ghrelin during basal and hyperinsulinemic conditions
Description
Effects of ghrelin on thirst, fluid intake, urine production and natriuresis
Time Frame
5 hours investigation day
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Otto L Jørgensen, Professor
Organizational Affiliation
University Hospital of Aarhus
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Aarhus
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
31608930
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.
Results Reference
derived
PubMed Identifier
28736944
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.
Results Reference
derived
Links:
URL
https://www.nature.com/articles/srep42706
Description
Original publication on the results from the study
Learn more about this trial
The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
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