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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: Detemir; Drug: Glargine; Drug: NPH

• Registration Number: NCT01461616
• Lead Sponsor: University of Aarhus

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.

Study Timeline

• Study First Submitted: 2011-10-24
• Study First Submitted QC: 2011-10-26
• Study First Posted: 2011-10-28
• Study Start: 2012-02
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-03
• Last Update Posted: 2012-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
detemir insulin injection	Detemir	insulin detemir will be injected in random order in one of three seperated visit days.
glargine insulin injection	Glargine	insulin glargine will be injected in random order in one of three seperated visit days.
NPH insulin injection	NPH	NPH insulin will be injected in random order in one of three seperated visit days.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.

Trial Locations

Locations (1)

Department of Endocrinology and Internal Medicine, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark