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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01461616
First received: October 24, 2011
Last updated: December 3, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: NPH
Drug: Detemir
Drug: Glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • IGF-I(ng/ml) [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    Hourly samples will be taken from 18:00 to 10:00 next day.

  • IGFBP-1(ng/ml) [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    Hourly samples will be taken from 18:00 to 10:00 next day.

  • IGFBP-2(ng/ml) [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    Hourly samples will be taken from 18:00 to 10:00 next day.

  • IGFBP-3(ng/ml) [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    Hourly samples will be taken from 18:00 to 10:00 next day.

  • Growth Hormone(ng/ml) [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 16 hours (from 18:00 to 10:00 next day) ] [ Designated as safety issue: No ]
    Hourly samples will be taken from 18:00 to 10:00 next day.


Enrollment: 19
Study Start Date: February 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NPH insulin injection
NPH insulin will be injected in random order in one of three seperated visit days.
Drug: NPH
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Name: NPH insulin: Insulatard
Experimental: detemir insulin injection
insulin detemir will be injected in random order in one of three seperated visit days.
Drug: Detemir
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Name: insulin Detemir: Levemir
Experimental: glargine insulin injection
insulin glargine will be injected in random order in one of three seperated visit days.
Drug: Glargine
equal doses of NPH insulin, insulin Detemir and insulin glargine injection
Other Name: insulin glargine: Lamtus

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01461616

Locations
Denmark
Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Aarhus, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Jens Sandahl Christiansen, M.D. Department of Endocrinology and Internal Medicine, Aarhus University Hospital
  More Information

Publications:

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01461616     History of Changes
Other Study ID Numbers: NPH-Detemir-Glargine-2011
Study First Received: October 24, 2011
Last Updated: December 3, 2012
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University of Aarhus:
Diabetes Mellitus, Type 1

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glargine
Insulin
Insulin, NPH
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014