Investigation of the Impact of Different Application Volumes of Insulin Aspart in Subjects With Type 1 Diabetes

This study has been completed.
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Pieber Thomas, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01399346
First received: May 23, 2011
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

Rationale: For the development of a closed loop system, faster insulin absorption after bolus administration could help to reduce the system's delay and thus increase patient safety. It has been shown that regular insulin absorption is faster when injecting insulin with a sprinkler needle (containing holes in the walls and being sealed at the tip). The current study will evaluate the impact of different application volumes on pharmacokinetic and pharmacodynamic properties of rapid acting insulin analogue (insulin aspart).

Objective: To compare the pharmacokinetic response (based on the time to maximum observed serum insulin concentration) and pharmacodynamic properties of rapid acting insulin aspart after subcutaneous injection of a defined dose (volume) at 1 versus 9 injection sites in patients with type 1 diabetes.

Study design: Monocentric, randomised, controlled, two-arm cross-over intervention study.

Population: Twelve type 1 diabetic subjects

Intervention: The investigational treatment is the subcutaneous administration of insulin aspart either as one bolus of 18 IU at one injection site or as 9 separately and simultaneously applied bolus of 2 IU each at 9 separate injection sites. Serum and 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 observed serum insulin aspart concentration.


Condition Intervention Phase
Type 1 Diabetes
Drug: Insulin aspart
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Single-center, Randomized, Controlled, 2-period Cross-over, Open-labelled Trial to Evaluate the Impact of Different Application Volumes on Pharmacokinetic and Pharmacodynamic Properties of Insulin Aspart in Subjects With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • tmax(ins), time to maximum observed serum insulin aspart concentration [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • t10%max(ins), time to reach 10% of maximum observed serum insulin aspart concentration [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: April 2011
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 bolus of insulin aspart 18 IU
Subcutaneous administration of insulin aspart as one bolus of 18 IU at one injection site.
Drug: Insulin aspart
Application of 18 IU insulin aspart as one bolus at one injection site
Experimental: 9 bolus of insulin aspart a 2 IU
Subcutaneous administration of insulin aspart as 9 separately and simultaneously applied bolus of 2 IU at 9 separate injection sites
Drug: Insulin aspart
Application of 18 IU insulin aspart as 9 bolus of 2 IU each at nine injection sites

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 20.0-28.0 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
  • 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 dosing.
  • 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 dosing visit.
  • Injection of NPH insulin or other intermediate-acting insulin products later than 12:00 hours (noon) on the day before the dosing 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 dosing visit.
  • Injection of any insulin later than 03:00 hours the night before the dosing visit.
  • Infusion of any insulin later than 03:00 hours the night before the dosing 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399346

Locations
Austria
Medical University of Graz
Graz, Austria, 8036
Sponsors and Collaborators
Medical University of Graz
European Commission
Investigators
Principal Investigator: Thomas R Pieber, MD Medical University of Graz
  More Information

Additional Information:
No publications provided

Responsible Party: Pieber Thomas, MD, MD, Prof. of Medicine, Medical University of Graz
ClinicalTrials.gov Identifier: NCT01399346     History of Changes
Other Study ID Numbers: SPRINK-01
Study First Received: May 23, 2011
Last Updated: April 19, 2012
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Graz:
Insulin aspart
Type 1 diabetes
Glucose clamp
Pharmacodynamics
Pharmacokinetics
Rapid Acting Insulin Analog

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin aspart
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014