search
Back to results

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

Primary Purpose

Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 3
Locations
Denmark
Study Type
Interventional
Intervention
NPH
Detemir
Glargine
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Department of Endocrinology and Internal Medicine, Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

NPH insulin injection

detemir insulin injection

glargine insulin injection

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

IGF-I(ng/ml)
Hourly samples will be taken 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.
IGFBP-2(ng/ml)
Hourly samples will be taken 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.
Growth Hormone(ng/ml)
Hourly samples will be taken from 18:00 to 10:00 next day.

Secondary Outcome Measures

plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine
Hourly samples will be taken 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
Hourly samples will be taken from 18:00 to 10:00 next day.

Full Information

First Posted
October 24, 2011
Last Updated
December 3, 2012
Sponsor
University of Aarhus
search

1. Study Identification

Unique Protocol Identification Number
NCT01461616
Brief Title
Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NPH insulin injection
Arm Type
Experimental
Arm Description
NPH insulin will be injected in random order in one of three seperated visit days.
Arm Title
detemir insulin injection
Arm Type
Experimental
Arm Description
insulin detemir will be injected in random order in one of three seperated visit days.
Arm Title
glargine insulin injection
Arm Type
Experimental
Arm Description
insulin glargine will be injected in random order in one of three seperated visit days.
Intervention Type
Drug
Intervention Name(s)
NPH
Other Intervention Name(s)
NPH insulin: Insulatard
Intervention Description
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Intervention Type
Drug
Intervention Name(s)
Detemir
Other Intervention Name(s)
insulin Detemir: Levemir
Intervention Description
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Intervention Type
Drug
Intervention Name(s)
Glargine
Other Intervention Name(s)
insulin glargine: Lamtus
Intervention Description
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Primary Outcome Measure Information:
Title
IGF-I(ng/ml)
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Title
IGFBP-1(ng/ml)
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Title
IGFBP-2(ng/ml)
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Title
IGFBP-3(ng/ml)
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Title
Growth Hormone(ng/ml)
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Secondary Outcome Measure Information:
Title
plasma glucose concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)
Title
insulin concentration (mmol/L) after a single injection of either NPH insulin, insulin Detemir or insulin glargine
Description
Hourly samples will be taken from 18:00 to 10:00 next day.
Time Frame
16 hours (from 18:00 to 10:00 next day)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Sandahl Christiansen, M.D.
Organizational Affiliation
Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Endocrinology and Internal Medicine, Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
11467325
Citation
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.
Results Reference
background
PubMed Identifier
10226799
Citation
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.
Results Reference
background
PubMed Identifier
17906644
Citation
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.
Results Reference
background
PubMed Identifier
17315038
Citation
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.
Results Reference
background
PubMed Identifier
7521354
Citation
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.
Results Reference
background
PubMed Identifier
9284701
Citation
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.
Results Reference
background
PubMed Identifier
8767170
Citation
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.
Results Reference
background
PubMed Identifier
11022197
Citation
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.
Results Reference
background
PubMed Identifier
10981882
Citation
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.
Results Reference
background
PubMed Identifier
15647580
Citation
Hirsch IB. Insulin analogues. N Engl J Med. 2005 Jan 13;352(2):174-83. doi: 10.1056/NEJMra040832. No abstract available.
Results Reference
background
PubMed Identifier
10220208
Citation
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.
Results Reference
background
PubMed Identifier
10866053
Citation
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.
Results Reference
background
PubMed Identifier
21055982
Citation
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.
Results Reference
background
PubMed Identifier
20730455
Citation
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.
Results Reference
background
PubMed Identifier
19470629
Citation
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.
Results Reference
background
PubMed Identifier
16842489
Citation
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs