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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Insulin, Globin Zinc
Isophane insulin, beef
Glargine
Insulin
Insulin, Isophane
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014