- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01461616
Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis
December 3, 2012 updated by: University of Aarhus
Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on IGFBP-1 Production and Serum IGF-I in Subjects With Type 1 Diabetes Mellitus: An Open-label, Randomised, Triple Cross-over Trial
The objective is to describe the interaction of equal doses of NPH insulin (Neutral Protamine Hagedorn), insulin Detemir and insulin glargine on IGFBP-1 (Insulin-like Growth Factor Binding Protein-1) production as well as immunoreactive and bioactive IGF-I (Insulin-like Growth Factor-I) after once-daily injection on three separate visits in type 1 diabetic subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Because of the importance of receptors activation and potential effects on the IGF system, a head-to-head comparison of the eventual differential impact of intermediate-acting human insulin (NPH), insulin detemir and insulin glargine on the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis is relevant to be conducted for the safety assurance of insulin analogues.
Therefore, this study aims to investigate whether the serum insulin profile obtained by once-daily injection of long-acting insulin analog, insulin detemir or insulin glargine, has a different impact on IGFBPs production and IGF-I concentrations (total IGF-I) bioactivity and tissue-availability as compared to that seen during treatment with intermediate-acting human insulin, NPH insulin.
Study Type
Interventional
Enrollment (Actual)
19
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Aarhus, Denmark, 8000
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Informed consent obtained before any trial-related activities.
- Diagnosis of diabetes mellitus according to WHO criteria; history and clinical course consistent with type 1 diabetes mellitus.
- Diagnosed with diabetes for more than 6 years and using continuous subcutaneous insulin infusion (CSII) at least 6 months at time of inclusion.
- Total daily insulin dose between 0.4 and 1.4 units/kg (both values included)
- HbA1c between 6% and 9% (both values included).
- Age ≥ 18 years.
- BMI between 18.5 and 28 kg /m2 (including both values).
Exclusion Criteria:
- Known or suspected allergy to trial product(s) or related products.
- Recurrent major hypoglycaemic episodes.
- Heart: Unstable Angina Pectoris, AMI < 12 months or heart insufficiency classified according to NYHA III-IV
- Blood Pressure: Severe uncontrolled hypertension with BP > 180/110 mmHg, sitting
- Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase > 2 x upper reference limit of the local laboratory.
- Kidneys: Impaired renal function corresponding to serum-creatinin > 150 μmol/l according to the local laboratory.
- Any disease judged by the investigator to affect the trial.
- Pregnancy, breast-feeding or the intention of becoming pregnant or fertile women not using adequate contraceptive measures - adequate contraceptive method is sterilisation, hysterectomy or current use of contraceptive pills or intra uterine device.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NPH insulin injection
NPH insulin will be injected in random order in one of three seperated visit days.
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equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Names:
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Experimental: detemir insulin injection
insulin detemir will be injected in random order in one of three seperated visit days.
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equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Names:
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Experimental: glargine insulin injection
insulin glargine will be injected in random order in one of three seperated visit days.
|
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
IGF-I(ng/ml)
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
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16 hours (from 18:00 to 10:00 next day)
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IGFBP-1(ng/ml)
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
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16 hours (from 18:00 to 10:00 next day)
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IGFBP-2(ng/ml)
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
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16 hours (from 18:00 to 10:00 next day)
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IGFBP-3(ng/ml)
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
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16 hours (from 18:00 to 10:00 next day)
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Growth Hormone(ng/ml)
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
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16 hours (from 18:00 to 10:00 next day)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine
Time Frame: 16 hours (from 18:00 to 10:00 next day)
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Hourly samples will be taken from 18:00 to 10:00 next day.
|
16 hours (from 18:00 to 10:00 next day)
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insulin concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine
Time Frame: 16 hours (from 18:00 to 10:00 next day)
|
Hourly samples will be taken from 18:00 to 10:00 next day.
|
16 hours (from 18:00 to 10:00 next day)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Jens Sandahl Christiansen, M.D., Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83. doi: 10.1056/NEJMra040832. No abstract available.
- Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes. 2000 Jun;49(6):999-1005. doi: 10.2337/diabetes.49.6.999.
- Thrailkill KM. Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility. Diabetes Technol Ther. 2000 Spring;2(1):69-80. doi: 10.1089/152091599316775.
- Bereket A, Lang CH, Wilson TA. Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus. Horm Metab Res. 1999 Feb-Mar;31(2-3):172-81. doi: 10.1055/s-2007-978716.
- Clemmons DR. Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov. 2007 Oct;6(10):821-33. doi: 10.1038/nrd2359.
- LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):302-10. doi: 10.1038/ncpendmet0427.
- Brismar K, Fernqvist-Forbes E, Wahren J, Hall K. Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes. J Clin Endocrinol Metab. 1994 Sep;79(3):872-8. doi: 10.1210/jcem.79.3.7521354.
- Janssen JA, Jacobs ML, Derkx FH, Weber RF, van der Lely AJ, Lamberts SW. Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1997 Sep;82(9):2809-15. doi: 10.1210/jcem.82.9.4180.
- Hanaire-Broutin H, Sallerin-Caute B, Poncet MF, Tauber M, Bastide R, Rosenfeld R, Tauber JP. Insulin therapy and GH-IGF-I axis disorders in diabetes: impact of glycaemic control and hepatic insulinization. Diabetes Metab. 1996 Jul;22(4):245-50.
- Ekman B, Nystrom F, Arnqvist HJ. Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes. Eur J Endocrinol. 2000 Oct;143(4):505-10. doi: 10.1530/eje.0.1430505.
- Bolli GB, Owens DR. Insulin glargine. Lancet. 2000 Aug 5;356(9228):443-5. doi: 10.1016/S0140-6736(00)02546-0. No abstract available.
- Heinemann L, Sinha K, Weyer C, Loftager M, Hirschberger S, Heise T. Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Diabet Med. 1999 Apr;16(4):332-8. doi: 10.1046/j.1464-5491.1999.00081.x.
- Varewijck AJ, Goudzwaard JA, Brugts MP, Lamberts SW, Hofland LJ, Janssen JA. Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir. Growth Horm IGF Res. 2010 Dec;20(6):427-31. doi: 10.1016/j.ghir.2010.10.002. Epub 2010 Nov 4.
- Vigneri R, Squatrito S, Sciacca L. Insulin and its analogs: actions via insulin and IGF receptors. Acta Diabetol. 2010 Dec;47(4):271-8. doi: 10.1007/s00592-010-0215-3. Epub 2010 Aug 21.
- Porcellati F, Rossetti P, Candeloro P, Lucidi P, Cioli P, Andreoli AM, Ghigo E, Bolli GB, Fanelli CG. Short-term effects of the long-acting insulin analog detemir and human insulin on plasma levels of insulin-like growth factor-I and its binding proteins in humans. J Clin Endocrinol Metab. 2009 Aug;94(8):3017-24. doi: 10.1210/jc.2008-2838. Epub 2009 May 26.
- Slawik M, Schories M, Busse Grawitz A, Reincke M, Petersen KG. Treatment with insulin glargine does not suppress serum IGF-1. Diabet Med. 2006 Jul;23(7):814-7. doi: 10.1111/j.1464-5491.2006.01863.x.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2012
Primary Completion (Actual)
November 1, 2012
Study Completion (Actual)
November 1, 2012
Study Registration Dates
First Submitted
October 24, 2011
First Submitted That Met QC Criteria
October 26, 2011
First Posted (Estimate)
October 28, 2011
Study Record Updates
Last Update Posted (Estimate)
December 4, 2012
Last Update Submitted That Met QC Criteria
December 3, 2012
Last Verified
December 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NPH-Detemir-Glargine-2011
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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