Absorption of Insulin Following Subcutaneous Bolus Administration With Different Bolus Durations

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

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

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Insulin LISPRO

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, A-8036
      • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tmax(GIR); time to maximum glucose infusion rate	8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
GIRmax, maximum glucose infusion rate	8 hours

Other Outcome Measures

Outcome Measure	Time Frame
tmax(ins), time to maximum observed plasma insulin lispro concentration	8 hours

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: European Commission
• Investigators: Principal Investigator: Thomas R Pieber, MD, Medical University of Graz, Internal Medicine, Endocrinology and Metabolism

Publications and helpful links

Helpful Links

• Medical University of Graz

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: February 13, 2013
• First Submitted That Met QC Criteria: February 13, 2013
• First Posted (Estimate): February 15, 2013

Study Record Updates

• Last Update Posted (Estimate): February 26, 2014
• Last Update Submitted That Met QC Criteria: February 25, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; glucose clamp; insulin bolus; insulin pump therapy; insulin lispro; rapid acting insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Lispro
• Other Study ID Numbers: CIPHER-Clamp