Growth Hormone DeficiencyPhase 4GHGMSNCT00929799
Growth Hormone and Glucose Metabolism
A Phase 4 study testing recombinant human Growth Hormone (Genotropin® ) in people with Growth Hormone Deficiency, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
The aim of the study is to investigate changes in insulin sensitivity and ß-cell function after 24 and 48 weeks of low-dose growth hormone (GH) therapy in adult patients with severe GH deficiency using highly standardized techniques. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Growth Hormone Deficiency
- What is being tested?
- recombinant human Growth Hormone (Genotropin® )
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2003to Aug 2007
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients >18 years old.
- Severe GH deficiency as diagnosed by an inadequate GH stimulation in three different tests:
- peak response < 3 µg/l during an insulin tolerance test;
- < 3 µg/l during glucagon test;
- < 9 µg/l during GHRH-arginine stimulation test).
Who cannot join
- GH replacement therapy prior to inclusion.
- History of diabetes Type 1 or 2.
- Biochemical evidence of impaired hepatic or renal function.
- History of cardiovascular disease.
- Uncontrolled hypertension.
- Current inflammatory or malignant disease.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Treatment With Human Growth Hormone on Insulin Resistance and Insulin Secretion in Adults With Growth Hormone Deficiency
The aim of the study is to investigate changes in insulin sensitivity and ß-cell function after 24 and 48 weeks of low-dose growth hormone (GH) therapy in adult patients with severe GH deficiency using highly standardized techniques. Insulin sensitivity was estimated using euglycemic, hyperinsulinemic clamps, while insulin secretion and hepatic insulin clearance were determined by changes in insulin and C-peptide levels during hyperglycemic hyperinsulinemic clamps with consecutive intravenous (i.v.) L-arginine stimulation tests. Moreover, the researchers investigated changes in body composition, lipolysis and cardiovascular risk markers. Furthermore, in order to verify the mechanisms involved in the pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin resistance under long term treatment, the researchers intend to establish changes in intramyocellular lipid (IMCL) in patients with GH deficiency by magnetic resonance (MR)-spectroscopy before and during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and insulin clearance. Finally, the researchers aim to justify the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.
Read the detailed description
In adult patients with GH deficiency, it is well documented that treatment with recombinant human GH results in a reduction of visceral fat mass and an increase in muscle mass. During long-term treatment, these effects seem to have beneficial effects on glucose metabolism. However, during the initial phase of GH treatment the insulin antagonistic effect of GH often induces an insulin resistant state which leads to an increase in insulin secretion or even, in cases with a preexisting ß-cell defect, to overt diabetes. Due to the lipolytic effect of GH, an impact of GH treatment on intracellular lipid homeostasis in adipose tissue, but also in skeletal muscle cells and liver cells can be expected. Moreover, since insulin resistance is known to be closely correlated with intramyocellular lipid (IMCL) content, changes in IMCL can play a key role in the GH-induced changes in the insulin sensitivity. Anyway, the mechanisms involved in the pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin resistance under long term treatment are presently not fully understood. In order to verify these mechanisms, we intend to establish changes in IMCL in patients with GH deficiency by MR-spectroscopy before and during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and insulin clearance. Finally, we aim to justify the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.
- Conditions
- Growth Hormone Deficiency
- Being tested
- recombinant human Growth Hormone (Genotropin® )
- Medical subject headings
- Dwarfism, Pituitary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human Growth Hormone (Genotropin® )Drug
Once daily by subcutaneous injection using a Genotropin pen in the abdomen at 22:00 h. Maximal GH dose of 0.003 mg/kg/day.
| Study group | Role | What they receive |
|---|---|---|
| Growth Hormone | Experimental | Therapy with recombinant human GH (Genotropin® 1 mg = 3 IU, Pfizer Inc., NY, USA) daily by subcutaneous injection using a Genotropin pen at maximal GH dose of 0.003 mg/kg/day in patients with severe GHD Receives: Drug: recombinant human Growth Hormone (Genotropin® ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in insulin sensitivity after 24 and 48 weeks of treatment with low GH dose in severely GH deficient patients.
Measured: At 24 and 48 weeks of treatment
Secondary outcomes (1)
Changes from baseline in insulin secretion and insulin clearance, as well as changes in body composition, lipolysis, cardiovascular risk markers, Adiponectin, IMCL and 11ßHSD activity.
Measured: At 24 and 48 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2009 (estimated)
- Study startNov 2003
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Growth Hormone DeficiencyStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Investigators
- Ayman M Arafat, Dr.med., Principal investigator, Charite Campus Benjamin Franklin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929799
- Sponsor's protocol ID
- NRA 6280012
- Other IDs
- EK218-01
- Acronym
- GHGMS
- Status last verified
- Jun 2009
- First submitted
- 29 Jun 2009
- Last updated
- 30 Jun 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Arafat AM, Mohlig M, Weickert MO, Schofl C, Spranger J, Pfeiffer AF. Improved insulin sensitivity, preserved beta cell function and improved whole-body glucose metabolism after low-dose growth hormone replacement therapy in adults with severe growth hormone deficiency: a pilot study. Diabetologia. 2010 Jul;53(7):1304-13. doi: 10.1007/s00125-010-1738-4. Epub 2010 Apr 6.
PubMed 20372873
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Treatment With Human Growth Hormone on Insulin Resistance and Insulin Secretion in Adults With Growth Hormone Deficiency
- ClinicalTrials.gov ID
- NCT00929799
- Acronym / sponsor ID
- GHGMS / NRA 6280012
- Conditions
- Growth Hormone Deficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Nov 2003
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 30 Jun 2009 (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.
The aim of the study is to investigate changes in insulin sensitivity and ß-cell function after 24 and 48 weeks of low-dose growth hormone (GH) therapy in adult patients with severe GH deficiency using highly standardized techniques. Insulin sensitivity was estimated using euglycemic, hyperinsulinemic clamps, while insulin secretion and hepatic insulin clearance were determined by changes in insulin and C-peptide levels during hyperglycemic hyperinsulinemic clamps with consecutive intravenous (i.v.) L-arginine stimulation tests. Moreover, the researchers investigated changes in body composition, lipolysis and cardiovascular risk markers. Furthermore, in order to verify the mechanisms involved in the pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin resistance under long term treatment, the researchers intend to establish changes in intramyocellular lipid (IMCL) in patients with GH deficiency by magnetic resonance (MR)-spectroscopy before and during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and insulin clearance. Finally, the researchers aim to justify the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.
Detailed description
In adult patients with GH deficiency, it is well documented that treatment with recombinant human GH results in a reduction of visceral fat mass and an increase in muscle mass. During long-term treatment, these effects seem to have beneficial effects on glucose metabolism. However, during the initial phase of GH treatment the insulin antagonistic effect of GH often induces an insulin resistant state which leads to an increase in insulin secretion or even, in cases with a preexisting ß-cell defect, to overt diabetes. Due to the lipolytic effect of GH, an impact of GH treatment on intracellular lipid homeostasis in adipose tissue, but also in skeletal muscle cells and liver cells can be expected. Moreover, since insulin resistance is known to be closely correlated with intramyocellular lipid (IMCL) content, changes in IMCL can play a key role in the GH-induced changes in the insulin sensitivity. Anyway, the mechanisms involved in the pathogenesis of GH-induced insulin resistance and the GH-induced improvement in insulin resistance under long term treatment are presently not fully understood. In order to verify these mechanisms, we intend to establish changes in IMCL in patients with GH deficiency by MR-spectroscopy before and during GH-treatment and to correlate IMCL with insulin resistance, insulin secretion and insulin clearance. Finally, we aim to justify the effect of GH on adiponectin secretion as well as on the 11-ß hydroxylase activity.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Growth Hormone | Experimental | Drug: recombinant human Growth Hormone (Genotropin® )Therapy with recombinant human GH (Genotropin® 1 mg = 3 IU, Pfizer Inc., NY, USA) daily by subcutaneous injection using a Genotropin pen at maximal GH dose of 0.003 mg/kg/day in patients with severe GHD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients >18 years old.
- Severe GH deficiency as diagnosed by an inadequate GH stimulation in three different tests:
Key exclusion criteria (7 listed)
- GH replacement therapy prior to inclusion.
- History of diabetes Type 1 or 2.
- Biochemical evidence of impaired hepatic or renal function.
- History of cardiovascular disease.
- Uncontrolled hypertension.
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 |
|---|---|---|
| recombinant human Growth Hormone (Genotropin® )Once daily by subcutaneous injection using a Genotropin pen in the abdomen at 22:00 h. Maximal GH dose of 0.003 mg/kg/day. | Drug | Growth Hormone |
Primary outcome
Change from baseline in insulin sensitivity after 24 and 48 weeks of treatment with low GH dose in severely GH deficient patients.
Time frame: At 24 and 48 weeks of treatment
1 secondary outcome
Changes from baseline in insulin secretion and insulin clearance, as well as changes in body composition, lipolysis, cardiovascular risk markers, Adiponectin, IMCL and 11ßHSD activity.
Time frame: At 24 and 48 weeks of treatment
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 Jun 2009.
- Derived from this study: PubMed 20372873Arafat AM, Mohlig M, Weickert MO, Schofl C, Spranger J, Pfeiffer AF. Improved insulin sensitivity, preserved beta cell function and improved whole-body glucose metabolism after low-dose growth hormone replacement therapy in adults with severe growth hormone deficiency: a pilot study. Diabetologia. 2010 Jul;53(7):1304-13. doi: 10.1007/s00125-010-1738-4. Epub 2010 Apr 6.
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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.
Ayman M Arafat, Dr.med. principal investigator
Charite Campus Benjamin Franklin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing recombinant human Growth Hormone (Genotropin® ) in people with Growth Hormone Deficiency, run by Charite University, Berlin, Germany at 1 site in Germany.
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 5 inclusion and 7 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 Jun 2009. 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 Germany. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change from baseline in insulin sensitivity after 24 and 48 weeks of treatment with low GH dose in severely GH deficient patients. (time frame: At 24 and 48 weeks of treatment). 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 NCT00929799, which also lists 1 linked publication.
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 Jun 2009.