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Diabetes Mellitus, Type 1Phase 3NCT01461616

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

A Phase 3 study testing NPH, Detemir and Glargine in people with Diabetes Mellitus, Type 1, run by University of Aarhus at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
NPH, Detemir and Glargine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteDenmark
Study dates
Feb 2012to Nov 2012
Phase
Phase 3
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Department of Endocrinology and Internal Medicine, Aarhus University Hospital

    Aarhus, 8000

Other trials in Denmark

About this study

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

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.

Read the 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.

Being tested
NPH, Detemir, Glargine
Keywords
Diabetes Mellitus, Type 1
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NPHDrug

    Also called NPH insulin: Insulatard

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

  • DetemirDrug

    Also called insulin Detemir: Levemir

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

  • GlargineDrug

    Also called insulin glargine: Lamtus

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

Study groups in NCT01461616
Study groupRoleWhat they receive
NPH insulin injectionExperimentalNPH insulin will be injected in random order in one of three seperated visit days.
Receives: Drug: NPH
detemir insulin injectionExperimentalinsulin detemir will be injected in random order in one of three seperated visit days.
Receives: Drug: Detemir
glargine insulin injectionExperimentalinsulin glargine will be injected in random order in one of three seperated visit days.
Receives: Drug: Glargine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. IGF-I(ng/ml)

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

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

  2. IGFBP-1(ng/ml)

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

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

  3. IGFBP-2(ng/ml)

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

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

  4. IGFBP-3(ng/ml)

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

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

  5. Growth Hormone(ng/ml)

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

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

Secondary outcomes (2)

  1. 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.

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

  2. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01461616
Sponsor's protocol ID
NPH-Detemir-Glargine-2011
Status last verified
Dec 2012
First submitted
24 Oct 2011
Last updated
4 Dec 2012
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 11467325

  • 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.

    PubMed 10226799

  • 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.

    PubMed 17906644

  • 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.

    PubMed 17315038

  • 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.

    PubMed 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.

    PubMed 9284701

  • 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.

    PubMed 8767170

  • 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.

    PubMed 11022197

  • 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.

    PubMed 10981882

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

    PubMed 15647580

  • 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.

    PubMed 10220208

  • 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.

    PubMed 10866053

  • 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.

    PubMed 21055982

  • 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.

    PubMed 20730455

  • 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.

    PubMed 19470629

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NPH, Detemir and Glargine in people with Diabetes Mellitus, Type 1, run by University of Aarhus at 1 site in Denmark.

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 7 inclusion and 8 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 4 Dec 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 Denmark. 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. 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?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

IGF-I(ng/ml) (time frame: 16 hours (from 18:00 to 10:00 next day)). The study lists 5 primary outcomes in all. 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 NCT01461616, which also lists 16 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 4 Dec 2012.

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