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

Sponsor

University of Aarhus (Other)

Overall Status

Completed

CT.gov ID

NCT01461616

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: NPH Drug: Detemir Drug: Glargine	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: insulin glargine: Lamtus

Arm

Intervention/Treatment

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 Names:

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 Names:

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 Names:

insulin glargine: Lamtus

Outcome Measures

Primary Outcome Measures

IGF-I(ng/ml) [16 hours (from 18:00 to 10:00 next day)]
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-1(ng/ml) [16 hours (from 18:00 to 10:00 next day)]
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-2(ng/ml) [16 hours (from 18:00 to 10:00 next day)]
Hourly samples will be taken from 18:00 to 10:00 next day.
IGFBP-3(ng/ml) [16 hours (from 18:00 to 10:00 next day)]
Hourly samples will be taken from 18:00 to 10:00 next day.
Growth Hormone(ng/ml) [16 hours (from 18:00 to 10:00 next day)]
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 [16 hours (from 18:00 to 10:00 next day)]
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 [16 hours (from 18:00 to 10:00 next day)]
Hourly samples will be taken from 18:00 to 10:00 next day.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.