Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis

NCT ID: NCT01461616

Last Updated: 2012-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2012-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 1

Keywords

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NPH insulin injection

NPH insulin will be injected in random order in one of three seperated visit days.

Group Type EXPERIMENTAL

NPH

Intervention Type DRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

detemir insulin injection

insulin detemir will be injected in random order in one of three seperated visit days.

Group Type EXPERIMENTAL

Detemir

Intervention Type DRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

glargine insulin injection

insulin glargine will be injected in random order in one of three seperated visit days.

Group Type EXPERIMENTAL

Glargine

Intervention Type DRUG

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

Interventions

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NPH

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

Intervention Type DRUG

Detemir

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

Intervention Type DRUG

Glargine

equal doses of NPH insulin, insulin Detemir and insulin glargine injection

Intervention Type DRUG

Other Intervention Names

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NPH insulin: Insulatard insulin Detemir: Levemir insulin glargine: Lamtus

Eligibility Criteria

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Inclusion Criteria

1. Informed consent obtained before any trial-related activities.
2. Diagnosis of diabetes mellitus according to WHO criteria; history and clinical course consistent with type 1 diabetes mellitus.
3. Diagnosed with diabetes for more than 6 years and using continuous subcutaneous insulin infusion (CSII) at least 6 months at time of inclusion.
4. Total daily insulin dose between 0.4 and 1.4 units/kg (both values included)
5. HbA1c between 6% and 9% (both values included).
6. Age ≥ 18 years.
7. BMI between 18.5 and 28 kg /m2 (including both values).

Exclusion Criteria

1. Known or suspected allergy to trial product(s) or related products.
2. Recurrent major hypoglycaemic episodes.
3. Heart: Unstable Angina Pectoris, AMI \< 12 months or heart insufficiency classified according to NYHA III-IV
4. Blood Pressure: Severe uncontrolled hypertension with BP \> 180/110 mmHg, sitting
5. Liver: Impaired hepatic function corresponding to serum-ALAT or basic phosphatase \> 2 x upper reference limit of the local laboratory.
6. Kidneys: Impaired renal function corresponding to serum-creatinin \> 150 μmol/l according to the local laboratory.
7. Any disease judged by the investigator to affect the trial.
8. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jens Sandahl Christiansen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Locations

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Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 11467325 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10226799 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17906644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17315038 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7521354 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9284701 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8767170 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11022197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10981882 (View on PubMed)

Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83. doi: 10.1056/NEJMra040832. No abstract available.

Reference Type BACKGROUND
PMID: 15647580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10220208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10866053 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21055982 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20730455 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19470629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16842489 (View on PubMed)

Other Identifiers

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NPH-Detemir-Glargine-2011

Identifier Type: -

Identifier Source: org_study_id