Absorption of Insulin Following Subcutaneous Bolus Administration With Different Bolus Durations

NCT01792323 | Completed Phase 1 DMC

• 1 other identifier: CIPHER-Clamp
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Type 1 Diabetes

Keywords

insulin pump therapy; insulin bolus; rapid acting insulin; insulin lispro; pharmacodynamics; pharmacokinetics; glucose clamp

Outcome Measures

Primary Outcomes (1)

• tmax(GIR); time to maximum glucose infusion rate

  8 hours

Secondary Outcomes (1)

• GIRmax, maximum glucose infusion rate

  8 hours

Other Outcomes (1)

• tmax(ins), time to maximum observed plasma insulin lispro concentration

  8 hours

Study Arms (2)

1 bolus of insulin lispro with short bolus duration

EXPERIMENTAL

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

Drug: Insulin LISPRO

1 bolus of insulin lispro with long bolus duration

EXPERIMENTAL

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

Drug: Insulin LISPRO

Interventions

Insulin LISPRO DRUG

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

1 bolus of insulin lispro with long bolus duration; 1 bolus of insulin lispro with short bolus duration

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• European Commission: collaborator

Study Sites (1)

Medical University of Graz

Graz, Styria, A-8036, Austria

Location

Related Links

• Medical University of Graz

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Thomas R Pieber, MD

  Medical University of Graz, Internal Medicine, Endocrinology and Metabolism

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Prof. of Medicine

Study Record Dates

• First Submitted: February 13, 2013
• First Posted: February 15, 2013
• Study Start: August 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: January 1, 2014
• Last Updated: February 26, 2014

Record last verified: 2014-02

Locations

AU (1)