MetabolismNCT01209416
The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
A study testing Acipimox and Ghrelin in people with Metabolism and Insulin Resistance, run by University of Aarhus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Metabolism, Insulin Resistance, Hypopituitarism
- What is being tested?
- Acipimox and Ghrelin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2012to Oct 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- males with hypopituitarism in regard to growth hormone and ACTH in stabile treatment regime
- age 18-65
- BMI 20-35
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Metabolism, Insulin Resistance, Hypopituitarism
- Being tested
- Acipimox, Ghrelin, Placebo
- Keywords
- ghrelin, metabolism, type 2 diabetes, insulin resistance
- Medical subject headings
- Insulin Resistance, Hypopituitarism, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcipimoxDrug
Also called Tablet Olbetam 250 mg
Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day
GhrelinDrug
Ghrelin infusion 4.2 ng/kg/min throughout the investigation day
PlaceboOther
Also called Placebo tablets, Saline infusion
placebo tablets or saline infusion
| Study group | Role | What they receive |
|---|---|---|
| Ghrelin / Acipimox | Active comparator | Ghrelin infusion and tablet acipimox Receives: Drug: Acipimox; Drug: Ghrelin |
| Ghrelin / placebo | Active comparator | Ghrelin infusion and placebo tablets Receives: Drug: Ghrelin; Other: Placebo |
| Placebo / Acipimox | Active comparator | saline infusion and tablet Acipimox Receives: Drug: Acipimox; Other: Placebo |
| Placebo / placebo | Placebo comparator | saline infusion and placebo tablets Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 hours investigation day
Effects of ghrelin during basal and hyperinsulinemic conditions
Effects of ghrelin on heart rate variability
Measured: 5 hours investigation day
Effects of ghrelin during basal and hyperinsulinemic conditions
Effects of ghrelin on thirst, fluid intake, urine production and natriuresis
Measured: 5 hours investigation day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2010 (estimated)
- Study startJun 2012
- Primary completionOct 2014
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MetabolismStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jens Otto L Jørgensen, Professor, Principal investigator, University Hospital of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01209416
- Sponsor's protocol ID
- M-2010-0157
- Status last verified
- May 2017
- First submitted
- 24 Sep 2010
- Last updated
- 30 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 31608930Vestergaard 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.
PubMed 28736944
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pharmacological Antilipolysis on the Metabolic Effects of Ghrelin
- ClinicalTrials.gov ID
- NCT01209416
- Acronym / sponsor ID
- M-2010-0157
- Conditions
- Metabolism, Insulin Resistance, Hypopituitarism
- Keywords
- ghrelin, metabolism, type 2 diabetes, insulin resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Jun 2012 (actual)
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ghrelin / Acipimox | Active comparator | Drug: Acipimox, Drug: GhrelinGhrelin infusion and tablet acipimox |
| Ghrelin / placebo | Active comparator | Drug: Ghrelin, Other: PlaceboGhrelin infusion and placebo tablets |
| Placebo / Acipimox | Active comparator | Drug: Acipimox, Other: Placebosaline infusion and tablet Acipimox |
| Placebo / placebo | Placebo comparator | Other: Placebosaline infusion and placebo tablets |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- males with hypopituitarism in regard to growth hormone and ACTH in stabile treatment regime
- age 18-65
- BMI 20-35
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcipimoxAlso: Tablet Olbetam 250 mgTablet Acipimox 250 mg administered 4 times previous to and during the investigation day | Drug | Ghrelin / Acipimox, Placebo / Acipimox |
| GhrelinGhrelin infusion 4.2 ng/kg/min throughout the investigation day | Drug | Ghrelin / Acipimox, Ghrelin / placebo |
| PlaceboAlso: Placebo tablets, Saline infusionplacebo tablets or saline infusion | Other | Ghrelin / placebo, Placebo / Acipimox, Placebo / placebo |
Primary outcome
Effects of ghrelin during basal and hyperinsulinemic conditions
Time frame: 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
Time frame: 5 hours investigation day
Effects of ghrelin on heart rate variability
Effects of ghrelin during basal and hyperinsulinemic conditions
Time frame: 5 hours investigation day
Effects of ghrelin on thirst, fluid intake, urine production and natriuresis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2017.
- Derived from this study: PubMed 31608930Jepsen 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.
- Derived from this study: PubMed 28736944Vestergaard 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.
- Original publication on the results from the studyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Otto L Jørgensen, Professor principal investigator
University Hospital of Aarhus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acipimox and Ghrelin in people with Metabolism and Insulin Resistance, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of ghrelin during basal and hyperinsulinemic conditions (time frame: 5 hours investigation day). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01209416, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2017.