Growth Hormone DeficiencyEarly Phase 1NCT00517062
Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates
A Early Phase 1 study testing Growth hormone (Genotropin) in people with Growth Hormone Deficiency, run by Oregon Health and Science University at 1 site in United States.
Trial summary
Study hypothesis: Growth hormone (GH), through its generation of free 'bioavailable' insulin-like growth factor (IGF)-I, can improve insulin sensitivity in adults with GH deficiency. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Growth Hormone Deficiency
- What is being tested?
- Growth hormone (Genotropin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2006to Jan 2012
- Phase
- Early Phase 1
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age range 18 to 75 years
- BMI should not exceed 40 kg/m2
- Confirmed GH deficient with at least one provocative test, e.g. insulin tolerance test and/ or GHRH/arginine
- Not received any GH therapy within last 6 months
- On a stable standardized hydrocortisone replacement dose regimen (twice a day at 8 AM and 4 PM),
- If any other pituitary hormone deficiencies are present, patient must be on optimal pituitary hormone replacement therapy, e.g. Thyroxine, testosterone and oestrogen replacement
- Normal renal and hepatic function
- Prepared to self-inject
Who cannot join
- Untreated or subclinically hypo/hyperthyroid
- Untreated or subclinically treated hypocortisolism
- Type 1 or 2 diabetes mellitus
- Subjects with evidence of nephropathy from any cause
- Subjects with evidence of retinopathy from any cause
- Any other medical illnesses that may affect the interpretation of the results
Show all 11Show fewer
- Pregnant
- Emotional/social instability likely to prejudice study completion
- Previous history of known malignancy
- Recurrent or severe unexplained hypoglycaemia
- Known or suspected drug/alcohol abuse
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health and Science University
Portland, Oregon, 97239
About this study
Official title: Effects of Low Dose Growth Hormone (GH) Therapy on Insulin Sensitivity, Adipocyte Insulin-like Growth Factor-I (IGF-I) and IGF-I/Insulin Receptor Density and Regulation of Cortisol Metabolism in GH Deficient Adults
Study hypothesis:
Growth hormone (GH), through its generation of free 'bioavailable' insulin-like growth factor (IGF)-I, can improve insulin sensitivity in adults with GH deficiency.
Read more
Study aims:
The purpose of this study is to determine the mechanism of how low dose GH treatment affects the body's sensitivity to insulin actions and whether this low GH dose can affect the body's handling of steroid hormone levels (cortisol clearance) in adults with GH deficiency.
Study design:
Men and women with confirmed GH deficiency, but not recently been on GH treatment will be invited to participate in this study. The subjects will be assessed at the initial visit to ascertain their suitability before further participating in the study. If suitable, an equal number of men and women will be randomized to receive either low dose GH or placebo injection for 3 months. Before, during and after treatment, the subjects will be assessed at regularly with blood tests, scans and fat biopsies. At the first and final visit, testing will include scans to measure the amount of whole body fat and fat in the stomach area, muscle, and liver; blood tests to measure levels of cortisol, and fat tissue (taken from a biopsy) analysis to measure the density of IGF-I in the muscle; whereas blood tests to examine insulin sensitivity will also be collected. This study will use Genotropin and Genotropin pen devices, and the the data will be analyzed using a computer statistical program where the identity of the subjects will be coded to maintain confidentiality.
Read the detailed description
The study will be double-blinded. One hundred subjects will be screened for eligibility initially, and 24 subjects will be enrolled with 12 subjects being randomized to receive the low GH dose (0.1 mg/day) treatment and 12 subjects to receive Placebo treatment for 3 months, allowing a 10% drop-out rate. The subjects will be taught by either by the Endocrine Nurse Specialists to self-administer the GH by subcutaneous injections using a Genotropin pen device.
Visit 1, Initial Screening Assessment (as out-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood glucose levels
Visit 2, Baseline Assessment (as in-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
- MRS, abdominal CT and DEXA scans
- One-step 3-hour hyperinsulinaemic euglycaemic clamp
- Cortisol production rates and urine cortisol collections
- Fat biopsies will be taken at the end of the assessment of cortisol production rates
Visit 3, Interim Assessment (Month 1) (as out-patient)
- Documentation of any adverse effects
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3
Visit 4, Final Assessment (Month 3) (as in-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
- MRS, abdominal CT and DEXA scans
- One-step 3-hour hyperinsulinaemic euglycaemic clamp
- Cortisol production rates and urine cortisol collections
- Fat biopsies will be taken at the end of the assessment of cortisol production rates
Any extra blood remaining from the samples of blood drawn may be banked indefinitely with confidential identifiers, and may be given to researchers in the future to examine for other potential causes of diabetes and heart diseases in adults. These blood samples, however, will not be used for genetic studies.
- Conditions
- Growth Hormone Deficiency
- Being tested
- Growth hormone (Genotropin), Placebo
- Keywords
- Growth hormone, insulin sensitivity, cortisol
- Medical subject headings
- Dwarfism, Pituitary, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growth hormone (Genotropin)Drug
Also called Genotropin
Growth hormone 0.1 mg self-injected once a day subcutaneously at bedtime.
PlaceboDrug
Also called Placebo.
Placebo self-injected once a day subcutaneously at bedtime.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Growth hormone Receives: Drug: Growth hormone (Genotropin) |
| B | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp
Measured: 3 months
Secondary outcomes (1)
Changes in fat IGF-I and IGF-I/insulin hybrid receptor density and body composition.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2007 (estimated)
- Study startJan 2006
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 Oregon Health and Science UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kevin Yuen, Oregon Health and Science University
- Investigators
- Jonathan Q. Purnell, MD, Principal investigator, Oregon Health and Science UniversityCharles T. Roberts, PhD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00517062
- Sponsor's protocol ID
- IRB1844
- Status last verified
- May 2012
- First submitted
- 15 Aug 2007
- Last updated
- 3 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yuen KC, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005 Oct;63(4):428-36. doi: 10.1111/j.1365-2265.2005.02359.x.
PubMed 16181235Yuen K, Frystyk J, Umpleby M, Fryklund L, Dunger D. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults. J Clin Endocrinol Metab. 2004 Aug;89(8):3956-64. doi: 10.1210/jc.2004-0300.
PubMed 15292333Yuen K, Wareham N, Frystyk J, Hennings S, Mitchell J, Fryklund L, Dunger D. Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance. Eur J Endocrinol. 2004 Jul;151(1):39-45. doi: 10.1530/eje.0.1510039.
PubMed 15248820Yuen KC, Roberts CT Jr, Frystyk J, Rooney WD, Pollaro JR, Klopfenstein BJ, Purnell JQ. Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency. J Clin Endocrinol Metab. 2014 Oct;99(10):E1862-9. doi: 10.1210/jc.2014-1532. Epub 2014 Jul 11.
PubMed 25013996
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Low Dose Growth Hormone (GH) Therapy on Insulin Sensitivity, Adipocyte Insulin-like Growth Factor-I (IGF-I) and IGF-I/Insulin Receptor Density and Regulation of Cortisol Metabolism in GH Deficient Adults
- ClinicalTrials.gov ID
- NCT00517062
- Acronym / sponsor ID
- IRB1844
- Conditions
- Growth Hormone Deficiency
- Keywords
- Growth hormone, insulin sensitivity, cortisol
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- Jan 2006
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 16 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.
Study hypothesis:
Growth hormone (GH), through its generation of free 'bioavailable' insulin-like growth factor (IGF)-I, can improve insulin sensitivity in adults with GH deficiency.
Study aims:
The purpose of this study is to determine the mechanism of how low dose GH treatment affects the body's sensitivity to insulin actions and whether this low GH dose can affect the body's handling of steroid hormone levels (cortisol clearance) in adults with GH deficiency.
Study design:
Men and women with confirmed GH deficiency, but not recently been on GH treatment will be invited to participate in this study. The subjects will be assessed at the initial visit to ascertain their suitability before further participating in the study. If suitable, an equal number of men and women will be randomized to receive either low dose GH or placebo injection for 3 months. Before, during and after treatment, the subjects will be assessed at regularly with blood tests, scans and fat biopsies. At the first and final visit, testing will include scans to measure the amount of whole body fat and fat in the stomach area, muscle, and liver; blood tests to measure levels of cortisol, and fat tissue (taken from a biopsy) analysis to measure the density of IGF-I in the muscle; whereas blood tests to examine insulin sensitivity will also be collected. This study will use Genotropin and Genotropin pen devices, and the the data will be analyzed using a computer statistical program where the identity of the subjects will be coded to maintain confidentiality.
Detailed description
The study will be double-blinded. One hundred subjects will be screened for eligibility initially, and 24 subjects will be enrolled with 12 subjects being randomized to receive the low GH dose (0.1 mg/day) treatment and 12 subjects to receive Placebo treatment for 3 months, allowing a 10% drop-out rate. The subjects will be taught by either by the Endocrine Nurse Specialists to self-administer the GH by subcutaneous injections using a Genotropin pen device.
Visit 1, Initial Screening Assessment (as out-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood glucose levels
Visit 2, Baseline Assessment (as in-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
- MRS, abdominal CT and DEXA scans
- One-step 3-hour hyperinsulinaemic euglycaemic clamp
- Cortisol production rates and urine cortisol collections
- Fat biopsies will be taken at the end of the assessment of cortisol production rates
Visit 3, Interim Assessment (Month 1) (as out-patient)
- Documentation of any adverse effects
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3
Visit 4, Final Assessment (Month 3) (as in-patient)
- Physical examination, weight, height, and waist circumference measurements
- Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
- MRS, abdominal CT and DEXA scans
- One-step 3-hour hyperinsulinaemic euglycaemic clamp
- Cortisol production rates and urine cortisol collections
- Fat biopsies will be taken at the end of the assessment of cortisol production rates
Any extra blood remaining from the samples of blood drawn may be banked indefinitely with confidential identifiers, and may be given to researchers in the future to examine for other potential causes of diabetes and heart diseases in adults. These blood samples, however, will not be used for genetic studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Growth hormone (Genotropin)Growth hormone |
| B | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age range 18 to 75 years
- BMI should not exceed 40 kg/m2
- Confirmed GH deficient with at least one provocative test, e.g. insulin tolerance test and/ or GHRH/arginine
- Not received any GH therapy within last 6 months
- On a stable standardized hydrocortisone replacement dose regimen (twice a day at 8 AM and 4 PM),
Key exclusion criteria (11 listed)
- Untreated or subclinically hypo/hyperthyroid
- Untreated or subclinically treated hypocortisolism
- Type 1 or 2 diabetes mellitus
- Subjects with evidence of nephropathy from any cause
- Subjects with evidence of retinopathy from any cause
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 |
|---|---|---|
| Growth hormone (Genotropin)Also: GenotropinGrowth hormone 0.1 mg self-injected once a day subcutaneously at bedtime. | Drug | A |
| PlaceboAlso: Placebo.Placebo self-injected once a day subcutaneously at bedtime. | Drug | B |
Primary outcome
Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp
Time frame: 3 months
1 secondary outcome
Changes in fat IGF-I and IGF-I/insulin hybrid receptor density and body composition.
Time frame: 3 months
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 3 May 2012.
- Background: PubMed 16181235Yuen KC, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005 Oct;63(4):428-36. doi: 10.1111/j.1365-2265.2005.02359.x.
- Background: PubMed 15292333Yuen K, Frystyk J, Umpleby M, Fryklund L, Dunger D. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults. J Clin Endocrinol Metab. 2004 Aug;89(8):3956-64. doi: 10.1210/jc.2004-0300.
- Background: PubMed 15248820Yuen K, Wareham N, Frystyk J, Hennings S, Mitchell J, Fryklund L, Dunger D. Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance. Eur J Endocrinol. 2004 Jul;151(1):39-45. doi: 10.1530/eje.0.1510039.
- Derived from this study: PubMed 25013996Yuen KC, Roberts CT Jr, Frystyk J, Rooney WD, Pollaro JR, Klopfenstein BJ, Purnell JQ. Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency. J Clin Endocrinol Metab. 2014 Oct;99(10):E1862-9. doi: 10.1210/jc.2014-1532. Epub 2014 Jul 11.
- American Endocrine SocietyLink 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.
Jonathan Q. Purnell, MD principal investigator
Oregon Health and Science University
Charles T. Roberts, PhD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Growth hormone (Genotropin) in people with Growth Hormone Deficiency, run by Oregon Health and Science University at 1 site in United States.
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 8 inclusion and 11 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 3 May 2012. 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 United States. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp (time frame: 3 months). 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 NCT00517062, which also lists 4 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 3 May 2012.