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

NCT01461616 | Completed Phase 3

• 1 other identifier: NPH-Detemir-Glargine-2011
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (5)

• IGF-I(ng/ml)

  Hourly samples will be taken from 18:00 to 10:00 next day.

  16 hours (from 18:00 to 10:00 next day)

• IGFBP-1(ng/ml)

  Hourly samples will be taken from 18:00 to 10:00 next day.

  16 hours (from 18:00 to 10:00 next day)

• IGFBP-2(ng/ml)

  Hourly samples will be taken from 18:00 to 10:00 next day.

  16 hours (from 18:00 to 10:00 next day)

• IGFBP-3(ng/ml)

  Hourly samples will be taken from 18:00 to 10:00 next day.

  16 hours (from 18:00 to 10:00 next day)

• Growth Hormone(ng/ml)

  Hourly samples will be taken from 18:00 to 10:00 next day.

  16 hours (from 18:00 to 10:00 next day)

Secondary Outcomes (2)

• plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine

  16 hours (from 18:00 to 10:00 next day)

• insulin concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine

  16 hours (from 18:00 to 10:00 next day)

Study Arms (3)

NPH insulin injection

EXPERIMENTAL

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

Drug: NPH

detemir insulin injection

EXPERIMENTAL

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

Drug: Detemir

glargine insulin injection

EXPERIMENTAL

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

Drug: Glargine

Interventions

NPH DRUG

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

Also known as: NPH insulin: Insulatard

NPH insulin injection

Detemir DRUG

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

Also known as: insulin Detemir: Levemir

detemir insulin injection

Glargine DRUG

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

Also known as: insulin glargine: Lamtus

glargine insulin injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Related Publications (16)

• 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.

  PMID: 11467325 BACKGROUND

• 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.

  PMID: 10226799 BACKGROUND

• 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.

  PMID: 17906644 BACKGROUND

• 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.

  PMID: 17315038 BACKGROUND

• 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.

  PMID: 7521354 BACKGROUND

• 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.

  PMID: 9284701 BACKGROUND

• 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.

  PMID: 8767170 BACKGROUND

• 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.

  PMID: 11022197 BACKGROUND

• 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.

  PMID: 10981882 BACKGROUND

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

  PMID: 15647580 BACKGROUND

• 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.

  PMID: 10220208 BACKGROUND

• 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.

  PMID: 10866053 BACKGROUND

• 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.

  PMID: 21055982 BACKGROUND

• 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.

  PMID: 20730455 BACKGROUND

• 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.

  PMID: 19470629 BACKGROUND

• 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.

  PMID: 16842489 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Isophane Insulin, Human; Insulin Detemir; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Isophane; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Insulin, Regular, Human; Insulin; Proinsulin; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jens Sandahl Christiansen, M.D.

  Department of Endocrinology and Internal Medicine, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: October 28, 2011
• Study Start: February 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: December 4, 2012

Record last verified: 2012-12

Locations

DK (1)