Absorption of Insulin Following Subcutaneous Bolus Administration With Different Bolus Durations

Sponsor

Medical University of Graz (Other)

Overall Status

Completed

CT.gov ID

NCT01792323

Collaborator

European Commission (Other)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To cover meal-related insulin requirements, insulin pumps allow insulin to be delivered at high rates over a short period of time (bolus delivery). The length of this period (bolus duration) usually depends on the chosen bolus size and on the used insulin pump model. This study will evaluate the impact of different bolus durations (i.e., durations commonly employed in commercially available insulin pumps: 2 and 40 seconds for delivering 1 Unit of insulin) on the pharmacokinetic and pharmacodynamic properties of an rapid-acting insulin analogue.

Objective: To evaluate in type 1 diabetic patients the pharmacodynamics and pharmacokinetics of rapid-acting insulin (insulin lispro) administered as subcutaneous boluses with different bolus durations.

Study design: Single-center, randomized, controlled, two-arm cross-over intervention study

Population: Twenty type 1 diabetic subjects

Intervention: The investigational treatment is the subcutaneous administration of insulin lispro either as one bolus of 15 IU over a period of 30s or as one bolus of 15 IU over a period of 10 min. Plasma samples to assess pharmacodynamic and pharmacokinetic properties will be taken during an 8-hour clamp experiment. Patients will undergo both investigational treatments in a randomized order; between the two clamp visits there will be a wash-out period of 5-21 days.

Main study endpoint: Time to maximum glucose infusion rate

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Drug: Insulin LISPRO	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Subcutaneous Insulin Absorption Following Bolus Administrations With an Insulin Pump - Comparison of Bolus Administrations With Different Bolus Durations

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Nov 1, 2011

Actual Study Completion Date :

Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 bolus of insulin lispro with short bolus duration Subcutaneous administration of insulin lispro as a bolus of 15 IU over a period of 30 seconds	Drug: Insulin LISPRO Administration of 15 IU of insulin lispro over a period of 30 seconds
Experimental: 1 bolus of insulin lispro with long bolus duration Subcutaneous administration of insulin lispro as a bolus of 15 IU over a period of 10 minutes	Drug: Insulin LISPRO Administration of 15 IU of insulin lispro over a period of 30 seconds

Arm

Intervention/Treatment

Experimental: 1 bolus of insulin lispro with short bolus duration

Subcutaneous administration of insulin lispro as a bolus of 15 IU over a period of 30 seconds

Drug: Insulin LISPRO

Administration of 15 IU of insulin lispro over a period of 30 seconds

Experimental: 1 bolus of insulin lispro with long bolus duration

Subcutaneous administration of insulin lispro as a bolus of 15 IU over a period of 10 minutes

Drug: Insulin LISPRO

Administration of 15 IU of insulin lispro over a period of 30 seconds

Outcome Measures

Primary Outcome Measures

tmax(GIR); time to maximum glucose infusion rate [8 hours]

Secondary Outcome Measures

GIRmax, maximum glucose infusion rate [8 hours]

Other Outcome Measures

tmax(ins), time to maximum observed plasma insulin lispro concentration [8 hours]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Informed consent obtained after being advised of the nature of the study
Male or female aged 18-60 years (both inclusive)
Type 1 diabetes treated with multiple daily insulin injection or continuous subcutaneous insulin infusion for 12 months
Fasting C-peptide < 0.3nmol/L
Body mass index 20.0-30.0 kg/m² (both inclusive)
HbA1c < 10%

Exclusion Criteria:

Female of childbearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods
Skin pathology or condition prohibiting needle insertion/insulin administration as judged by the investigator
History of bleeding disorder
Current participation in another clinical study
Use of insulin lispro >2 weeks
Significant acute or chronic illness that might interfere with subject safety or integrity of results as judged by the investigator
Smoker (defined as >5 cigarettes/d)
Lipodystrophy
Current treatment with systemic (oral or i.v.) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, growth hormone, herbal products or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months
Significant history of alcoholism or drug abuse or a positive result in urine drug/alcohol screen

Study Day Exclusion Criteria:

Strenuous exercise within the last 24 hours prior to the clamp visit
Non-fasting (i.e. consumption of food or beverages, other than water, later than 22:00 hours the evening before the visit) except if slight intake of rapidly absorbable carbohydrates has been necessary in order to prevent hypoglycaemia
Injection of long-acting insulin (e.g. insulin glargine or insulin detemir) later than 12:00 hours (noon), 2 days before the clamp visit
Injection of NPH insulin or other intermediate-acting insulin products later than 12:00 hours (noon) on the day before the clamp visit
Injection of any short acting insulin (aspart, lispro, glulisine) or more than 6 IU of human insulin between 22:00 hours and 03:00 hours the night before the clamp visit
Injection of any insulin later than 03:00 hours the night before the clamp visit
Infusion of any insulin later than 03:00 hours the night before the clamp visit for subjects using continuous subcutaneous insulin infusion (CSII)
Positive result of alcohol breath test
Any medical condition that, in the opinion of the Investigator, could interfere with insulin pharmacokinetics and/or glucose metabolism