Intracellular Signaling Peptides and ProteinsNCT00512473
Growth Hormone Signaling in Vivo in Humans
A study testing Saline infusion, Human Growth Hormone and Pegvisomant in people with Intracellular Signaling Peptides and Proteins, run by University of Aarhus at 1 site in Denmark.
Trial summary
Objective: GH induces insulin resistance in muscle and fat and in vitro data indicate that this may involve crosstalk between the signaling pathways of the two hormones. Aim: To investigate GH and insulin signaling in vivo in human muscle and fat tissue in response to GH, GH receptor blockade and insulin stimulation.. Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Intracellular Signaling Peptides and Proteins
- What is being tested?
- Saline infusion, Human Growth Hormone and Pegvisomant
- Type of treatment
- 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
- Sep 2005to Apr 2006
- 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 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male
- Healthy
- Not taking medication
Who cannot join
- Insulin resistance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Growth Hormone (GH) Signaling in Vivo in Human Muscle and Adipose Tissue: Impact of Insulin, Substrate Background and gh Receptor Blockade
Objective: GH induces insulin resistance in muscle and fat and in vitro data indicate that this may involve crosstalk between the signaling pathways of the two hormones.
Aim: To investigate GH and insulin signaling in vivo in human muscle and fat tissue in response to GH, GH receptor blockade and insulin stimulation..
Read the detailed description
The molecular mechanisms by which GH promotes insulin antagonism are still unclear. Stimulation of lipolysis could be of importance since high plasma FFA levels have been shown to interfere with insulin receptor signaling via inhibition of insulin-stimulated insulin receptor substrate (IRS)-1 associated phosphatidylinositol (PI) 3-kinase activity in human skeletal muscle, resulting in a decreased GLUT4 translocation and glucose transport (6). A recent study, however, was unable to document a suppression in the insulin-stimulated activity of either IRS-1 associated PI 3-kinase or the serin/threonin kinase Akt after GH administration to healthy humans, despite induction of lipolysis and insulin resistance (7). Other studies have shown that acute GH exposure induces insulin resistance in skeletal muscle rapidly and before the subsequent rise in plasma FFA (1;7;8). These observations indicate that GH may cause insulin resistance via a non-FFA mediated mechanism.
The predominant GH signal transduction cascade comprises activation of the GHR dimer, phosphorylation of JAK2 and subsequently activation of Stat5. The intact JAK2/Stat5 pathway is necessary for normal statural growth (9). There is animal and in vitro evidence to suggest that insulin and GH share post-receptor signaling pathways (10). Convergence has been reported at the levels of Stat5 and SOCS3 as well as on protein kinases comprising the major IR signaling pathway; IRS 1/2, PI 3-kinase, Akt and ERK 1/2 (11-14).
Pegvisomant is a GH analog and a competitive reversible GH receptor antagonist, which blocks peripheral GH signal transduction (15). Pegvisomant has been shown to inhibit the necessary conformational change of the GHR dimer and thus constitutes an optimal negative control in GH signaling studies.
The aim of this work was to further study GH signal transduction pathways in vivo in muscle and adipose tissue from healthy subjects in response to acute and more prolonged GH exposure as well as during hyperinsulinemia. The design also included administration of pegvisomant in an attempt to correct for spontaneous GH secretion.
- Being tested
- Saline infusion, Human Growth Hormone, Pegvisomant
- Keywords
- GH, GH receptor blockade, GH signaling, insulin resistance
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saline infusionDrug
0.9 % NaCl
Human Growth HormoneDrug
0.5 mg genotropin administered as a bolus at t = 0
PegvisomantDrug
30 mg Somavert administered at t = - 36 hours
| Study group | Role | What they receive |
|---|---|---|
| A | Placebo comparator | I.v. saline for 8 hours Receives: Drug: Saline infusion |
| GH | Experimental | Growth hormone (0.5 mg s.c. at t = 0 hours) Receives: Drug: Human Growth Hormone |
| Pegvisomant | Experimental | Pegvisomant injection 30 mg 36 hours prior to the study Receives: Drug: Pegvisomant |
What is being measured
The primary outcome is the main question the study is designed to answer.
GH-receptor signaling
Measured: hours
Secondary outcomes (1)
Insulin sensitivity
Measured: hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2007 (estimated)
- Study startSep 2005
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Intracellular Signaling Peptides and ProteinsStudies 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
- Single blind
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Investigators
- Lars C Gormsen, MD, Principal investigator, Aarhus University Hospital, Department M
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512473
- Sponsor's protocol ID
- 20050113
- Status last verified
- Aug 2007
- First submitted
- 6 Aug 2007
- Last updated
- 7 Aug 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Gormsen LC, Nielsen C, Gjedsted J, Gjedde S, Vestergaard ET, Christiansen JS, Jorgensen JO, Moller N. Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans. Clin Endocrinol (Oxf). 2007 May;66(5):641-5. doi: 10.1111/j.1365-2265.2007.02786.x.
PubMed 17492951Gormsen LC, Nielsen C, Jessen N, Jorgensen JO, Moller N. Time-course effects of physiological free fatty acid surges on insulin sensitivity in humans. Acta Physiol (Oxf). 2011 Mar;201(3):349-56. doi: 10.1111/j.1748-1716.2010.02181.x. Epub 2010 Oct 11.
PubMed 20731625Nielsen C, Gormsen LC, Jessen N, Pedersen SB, Moller N, Lund S, Jorgensen JO. Growth hormone signaling in vivo in human muscle and adipose tissue: impact of insulin, substrate background, and growth hormone receptor blockade. J Clin Endocrinol Metab. 2008 Jul;93(7):2842-50. doi: 10.1210/jc.2007-2414. Epub 2008 May 6.
PubMed 18460563
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Growth Hormone (GH) Signaling in Vivo in Human Muscle and Adipose Tissue: Impact of Insulin, Substrate Background and gh Receptor Blockade
- ClinicalTrials.gov ID
- NCT00512473
- Acronym / sponsor ID
- 20050113
- Keywords
- GH, GH receptor blockade, GH signaling, insulin resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Sep 2005
- Study completion
- Apr 2006 (actual)
- First posted
- 7 Aug 2007 (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.
Objective: GH induces insulin resistance in muscle and fat and in vitro data indicate that this may involve crosstalk between the signaling pathways of the two hormones.
Aim: To investigate GH and insulin signaling in vivo in human muscle and fat tissue in response to GH, GH receptor blockade and insulin stimulation..
Detailed description
The molecular mechanisms by which GH promotes insulin antagonism are still unclear. Stimulation of lipolysis could be of importance since high plasma FFA levels have been shown to interfere with insulin receptor signaling via inhibition of insulin-stimulated insulin receptor substrate (IRS)-1 associated phosphatidylinositol (PI) 3-kinase activity in human skeletal muscle, resulting in a decreased GLUT4 translocation and glucose transport (6). A recent study, however, was unable to document a suppression in the insulin-stimulated activity of either IRS-1 associated PI 3-kinase or the serin/threonin kinase Akt after GH administration to healthy humans, despite induction of lipolysis and insulin resistance (7). Other studies have shown that acute GH exposure induces insulin resistance in skeletal muscle rapidly and before the subsequent rise in plasma FFA (1;7;8). These observations indicate that GH may cause insulin resistance via a non-FFA mediated mechanism.
The predominant GH signal transduction cascade comprises activation of the GHR dimer, phosphorylation of JAK2 and subsequently activation of Stat5. The intact JAK2/Stat5 pathway is necessary for normal statural growth (9). There is animal and in vitro evidence to suggest that insulin and GH share post-receptor signaling pathways (10). Convergence has been reported at the levels of Stat5 and SOCS3 as well as on protein kinases comprising the major IR signaling pathway; IRS 1/2, PI 3-kinase, Akt and ERK 1/2 (11-14).
Pegvisomant is a GH analog and a competitive reversible GH receptor antagonist, which blocks peripheral GH signal transduction (15). Pegvisomant has been shown to inhibit the necessary conformational change of the GHR dimer and thus constitutes an optimal negative control in GH signaling studies.
The aim of this work was to further study GH signal transduction pathways in vivo in muscle and adipose tissue from healthy subjects in response to acute and more prolonged GH exposure as well as during hyperinsulinemia. The design also included administration of pegvisomant in an attempt to correct for spontaneous GH secretion.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Placebo comparator | Drug: Saline infusionI.v. saline for 8 hours |
| GH | Experimental | Drug: Human Growth HormoneGrowth hormone (0.5 mg s.c. at t = 0 hours) |
| Pegvisomant | Experimental | Drug: PegvisomantPegvisomant injection 30 mg 36 hours prior to the study |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Male
- Healthy
- Not taking medication
Key exclusion criteria (1 listed)
- Insulin resistance
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 |
|---|---|---|
| Saline infusion0.9 % NaCl | Drug | A |
| Human Growth Hormone0.5 mg genotropin administered as a bolus at t = 0 | Drug | GH |
| Pegvisomant30 mg Somavert administered at t = - 36 hours | Drug | Pegvisomant |
Primary outcome
GH-receptor signaling
Time frame: hours
1 secondary outcome
Insulin sensitivity
Time frame: hours
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 7 Aug 2007.
- Results publication: PubMed 17492951Gormsen LC, Nielsen C, Gjedsted J, Gjedde S, Vestergaard ET, Christiansen JS, Jorgensen JO, Moller N. Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans. Clin Endocrinol (Oxf). 2007 May;66(5):641-5. doi: 10.1111/j.1365-2265.2007.02786.x.
- Derived from this study: PubMed 20731625Gormsen LC, Nielsen C, Jessen N, Jorgensen JO, Moller N. Time-course effects of physiological free fatty acid surges on insulin sensitivity in humans. Acta Physiol (Oxf). 2011 Mar;201(3):349-56. doi: 10.1111/j.1748-1716.2010.02181.x. Epub 2010 Oct 11.
- Derived from this study: PubMed 18460563Nielsen C, Gormsen LC, Jessen N, Pedersen SB, Moller N, Lund S, Jorgensen JO. Growth hormone signaling in vivo in human muscle and adipose tissue: impact of insulin, substrate background, and growth hormone receptor blockade. J Clin Endocrinol Metab. 2008 Jul;93(7):2842-50. doi: 10.1210/jc.2007-2414. Epub 2008 May 6.
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.
Lars C Gormsen, MD principal investigator
Aarhus University Hospital, Department M
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Saline infusion, Human Growth Hormone and Pegvisomant in people with Intracellular Signaling Peptides and Proteins, 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 1 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 7 Aug 2007. 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?
GH-receptor signaling (time frame: hours). 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 NCT00512473, which also lists 3 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 7 Aug 2007.