Insulin by Jet-injection for Hyperglycemia in Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University Medical Center Nijmegen
Sponsor:
Information provided by (Responsible Party):
HM de Wit, University Medical Center Nijmegen
ClinicalTrials.gov Identifier:
NCT01947556
First received: September 2, 2013
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to compare the pharmacokinetic and pharmacodynamic profile of the rapid-acting insulin analogue aspart (Novorapid®) injected subcutaneously by jet-injection to that of the same insulin injected with a conventional pen in the management of hyperglycemia in subjects with diabetes


Condition Intervention
Diabetes Mellitus
Drug: insulin aspart

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Rapid-acting Insulin Injected by Needle-free Jet-injection in the Management of Hyperglycemia in Patients With Diabetes

Resource links provided by NLM:


Further study details as provided by University Medical Center Nijmegen:

Primary Outcome Measures:
  • T-BG≥10 [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the time in minutes until plasma glucose concentration has dropped with ≥ 10mmol/l (T-BG≥10).


Secondary Outcome Measures:
  • T-BG5 and 8 (min) [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the time in minutes until plasma glucose values drop below 8 an 5 mmol/l, respectively

  • Rfall [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the slope of the glucose fall (mmol • l-1 • min-1), calculated from the time- glucose curve

  • BG-AUC 0-2h [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the area under the time-glucose curve, reflecting post-injection hyperglycaemic burden, from 0 to 2h after insulin injection.

  • BG-AUC 0-6h [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the area under the time-glucose curve (mmol • min-1 • l-1), from 0 to 6h after insulin injection.

  • C-INSmax (pmol/l) [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    maximal insulin concentration

  • T-INSmax [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    time to maximal insulin concentration in minutes(C-INSmax)

  • T-INSBL [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    the time until plasma insulin values drop below baseline values (minutes)

  • INSAUC [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    area under the insulin concentration curve (pmol • min-1 • l-1)(from timepoint 0), reflects total insulin absorption

  • T-INSAUC50% [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    time until 50% of insulin absorption in minutes(mean residence time, MRT)


Other Outcome Measures:
  • NRS pain [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: No ]
    The amount of discomfort or pain and the ease of use experienced with the two administration methods using a numeric rating scale from 0 to 10 (will be administered 30 minutes after insulin administration)

  • hypoglycaemia [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: Yes ]
    Number of patients requiring exogenous glucose infusion to prevent hypoglycaemia (blood glucose ≤3.9 mmol/l) after insulin injection;

  • exogenous glucose [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: Yes ]
    Amount of exogenous glucose required to prevent hypoglycaemia after insulin injection

  • time exogenous glucose requirement [ Time Frame: participants will be followed for the duration of the study, an expected average of 4 weeks ] [ Designated as safety issue: Yes ]
    Duration of time that exogenous glucose is required to prevent hypoglycaemia after insulin injection.


Estimated Enrollment: 20
Study Start Date: March 2014
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
insujet is tested first
first procedure: experiment with the investigational product (Insujet pen)containing insulin aspart; second procedure: control device (conventional Novopen III insulin pen) contains insulin aspart.
Drug: insulin aspart
After hyperglycaemia (18-23 mmol/l) has been reached (by decreasing or interrupting exogenous insulin administration 12-24 hours before the experiment), aspart insulin (in a dose of 1.5 times the amount of insulin needed to reduce blood glucose to 6 mmol/l calculated by the insulin-sensitivity factor) and a similar volume of placebo solution will be administered subcutaneously by Insujet pen and conventional insulin pen, respectively, or vice versa. The injections will be given simultaneously by the subject under supervision of the research staff.
Other Name: Novorapid
insujet is tested second
first procedure: experiment with the conventional Novopen III insulin pen containing insulin aspart; second procedure: investigational device (Insujet) contains insulin aspart.
Drug: insulin aspart
After hyperglycaemia (18-23 mmol/l) has been reached (by decreasing or interrupting exogenous insulin administration 12-24 hours before the experiment), aspart insulin (in a dose of 1.5 times the amount of insulin needed to reduce blood glucose to 6 mmol/l calculated by the insulin-sensitivity factor) and a similar volume of placebo solution will be administered subcutaneously by Insujet pen and conventional insulin pen, respectively, or vice versa. The injections will be given simultaneously by the subject under supervision of the research staff.
Other Name: Novorapid

Detailed Description:

Recently, we showed in both healthy, non-diabetic volunteers and in patients with type 1 (T1DM) and insulin-treated type 2 diabetes (T2DM) a 40-50% faster absorption of rapid-acting insulin analogues when administered by jet injection technology rather than by conventional insulin pen. The faster insulin action of insulin administration by jet injection may be especially advantageous for correction of hyperglycemia.

To investigate this, a open-label randomised controlled cross-over study will be performed in 20 adult patients (18-75 years) with T1DM or T2DM on basal-bolus insulin treatment.

The pharmacokinetic and pharmacodynamic profile of insulin aspart will be derived from the time-action profiles of insulin and glucose, respectively, in response to insulin (in a dose of 1.5 times the amount of insulin needed to reduce blood glucose to 6 mmol/l calculated by the insulin-sensitivity factor) after reaching hyperglycemia (18-23 mmol/l). All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject insulin, and on the other occasion insulin will be injected with a conventional insulin pen. The order of these occasions will be randomised. Both devices will be operated by the patient after sufficient training. Ease of use will be evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diabetes mellitus type 1 or 2
  • Age 18-75 years
  • Body-Mass Index ≥25 kg/m2 and ≤40 kg/m2
  • Stable glycaemic control with HbA1c ≥48 (6.5%) and ≤86 mmol/mol (10%)
  • Insulin treatment according to basal-bolus regimen, i.e. by multiple daily injections at least four times daily, or by subcutaneous insulin pump, for at least 12 months, use of metformin allowed

Exclusion Criteria:

  • Inability to provide informed consent
  • Insulin requirement of <34 or >200 units per day
  • Treatment with systemic corticosteroids, immunosuppressive or cytostatic drugs
  • Known allergy to aspart insulin
  • Use of oral antidiabetic drugs other than metformin
  • Symptomatic diabetic neuropathy
  • History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) in the previous 6 months
  • Pregnancy or the intention to become pregnant
  • Renal disease (creatinine >150 μmol/l or MDRD-GFR <30 ml/min/1.73m2)
  • Liver disease (aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range)
  • Presence of any other medical condition that might interfere with the study protocol
  • anemia
  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: NCT01947556

Contacts
Contact: Helena de Wit, MD +31 24 36 18819 h.dewit@aig.umcn.nl
Contact: Bastiaan de Galan, MD, PhD b.degalan@aig.umcn.nl

Locations
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands, 6500HB
Sub-Investigator: Helena de Wit, MD         
Sponsors and Collaborators
University Medical Center Nijmegen
Investigators
Study Chair: Bastiaan de Galan, MD PhD Radboud University
  More Information

No publications provided

Responsible Party: HM de Wit, MD, University Medical Center Nijmegen
ClinicalTrials.gov Identifier: NCT01947556     History of Changes
Other Study ID Numbers: PKPD_INSJ_3
Study First Received: September 2, 2013
Last Updated: March 17, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Center Nijmegen:
diabetes
insulin administration
hyperglycaemia
insulin aspart

Additional relevant MeSH terms:
Insulin, Globin Zinc
Insulin
Insulin Aspart
Diabetes Mellitus
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014