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

University of Aarhus

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Glargine; Drug: Detemir; Drug: NPH

Study type: Interventional

Funder types: Other

Identifiers

NCT01461616

NPH-Detemir-Glargine-2011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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19 participants in 3 patient groups

NPH insulin injection

Experimental group

Description:

NPH insulin will be injected in random order in one of three seperated visit days.

Treatment:

Drug: NPH

detemir insulin injection

Experimental group

Description:

insulin detemir will be injected in random order in one of three seperated visit days.

Treatment:

Drug: Detemir

glargine insulin injection

Experimental group

Description:

insulin glargine will be injected in random order in one of three seperated visit days.

Treatment:

Drug: Glargine