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Insulin by Jet-injection for Hyperglycemia in Diabetes

Primary Purpose

Diabetes Mellitus

Status

Completed

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

insulin aspart

About this trial

This is an interventional treatment trial for Diabetes Mellitus focused on measuring diabetes, insulin administration, hyperglycaemia, insulin aspart

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Radboud University Nijmegen Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

insujet is tested first

insujet is tested second

Arm Description

first procedure: experiment with the investigational product (Insujet pen)containing insulin aspart; second procedure: control device (conventional Novopen III insulin pen) contains insulin aspart.

first procedure: experiment with the conventional Novopen III insulin pen containing insulin aspart; second procedure: investigational device (Insujet) contains insulin aspart.

Outcomes

Primary Outcome Measures

T-BG≥10

the time in minutes until plasma glucose concentration has dropped with ≥ 10mmol/l (T-BG≥10).

Secondary Outcome Measures

T-BG5 and 8 (min)

the time in minutes until plasma glucose values drop below 8 an 5 mmol/l, respectively

Rfall

the slope of the glucose fall (mmol • l-1 • min-1), calculated from the time- glucose curve

BG-AUC 0-2h

the area under the time-glucose curve, reflecting post-injection hyperglycaemic burden, from 0 to 2h after insulin injection.

BG-AUC 0-6h

the area under the time-glucose curve (mmol • min-1 • l-1), from 0 to 6h after insulin injection.

C-INSmax (pmol/l)

maximal insulin concentration

T-INSmax

time to maximal insulin concentration in minutes(C-INSmax)

T-INSBL

the time until plasma insulin values drop below baseline values (minutes)

INSAUC

area under the insulin concentration curve (pmol • min-1 • l-1)(from timepoint 0), reflects total insulin absorption

T-INSAUC50%

time until 50% of insulin absorption in minutes(mean residence time, MRT)

Full Information

NCT ID

NCT01947556

First Posted

September 2, 2013

Last Updated

November 25, 2014

Sponsor

University Medical Center Nijmegen

1. Study Identification

Unique Protocol Identification Number

NCT01947556

Brief Title

Insulin by Jet-injection for Hyperglycemia in Diabetes

Official Title

The Effect of Rapid-acting Insulin Injected by Needle-free Jet-injection in the Management of Hyperglycemia in Patients With Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

March 2014 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Medical Center Nijmegen

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus

Keywords

diabetes, insulin administration, hyperglycaemia, insulin aspart

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

insujet is tested first

Arm Type

Other

Arm Description

first procedure: experiment with the investigational product (Insujet pen)containing insulin aspart; second procedure: control device (conventional Novopen III insulin pen) contains insulin aspart.

Arm Title

insujet is tested second

Arm Type

Other

Arm Description

first procedure: experiment with the conventional Novopen III insulin pen containing insulin aspart; second procedure: investigational device (Insujet) contains insulin aspart.

Intervention Type

Drug

Intervention Name(s)

insulin aspart

Other Intervention Name(s)

Novorapid

Intervention Description

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) will be administered subcutaneously by Insujet pen or conventional insulin pen, on two separate occasions, or vice versa. The injection will be given by the subject under supervision of the research staff.

Primary Outcome Measure Information:

Title

T-BG≥10

Description

the time in minutes until plasma glucose concentration has dropped with ≥ 10mmol/l (T-BG≥10).

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Secondary Outcome Measure Information:

Title

T-BG5 and 8 (min)

Description

the time in minutes until plasma glucose values drop below 8 an 5 mmol/l, respectively

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

Rfall

Description

the slope of the glucose fall (mmol • l-1 • min-1), calculated from the time- glucose curve

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

BG-AUC 0-2h

Description

the area under the time-glucose curve, reflecting post-injection hyperglycaemic burden, from 0 to 2h after insulin injection.

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

BG-AUC 0-6h

Description

the area under the time-glucose curve (mmol • min-1 • l-1), from 0 to 6h after insulin injection.

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

C-INSmax (pmol/l)

Description

maximal insulin concentration

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

T-INSmax

Description

time to maximal insulin concentration in minutes(C-INSmax)

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

T-INSBL

Description

the time until plasma insulin values drop below baseline values (minutes)

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

INSAUC

Description

area under the insulin concentration curve (pmol • min-1 • l-1)(from timepoint 0), reflects total insulin absorption

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

T-INSAUC50%

Description

time until 50% of insulin absorption in minutes(mean residence time, MRT)

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Other Pre-specified Outcome Measures:

Title

NRS pain

Description

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)

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

hypoglycaemia

Description

Number of patients requiring exogenous glucose infusion to prevent hypoglycaemia (blood glucose ≤3.9 mmol/l) after insulin injection;

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

exogenous glucose

Description

Amount of exogenous glucose required to prevent hypoglycaemia after insulin injection

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

Title

time exogenous glucose requirement

Description

Duration of time that exogenous glucose is required to prevent hypoglycaemia after insulin injection.

Time Frame

participants will be followed for the duration of the study, an expected average of 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bastiaan de Galan, MD PhD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Study Chair

Facility Information:

Facility Name

Radboud University Nijmegen Medical Centre

City

Nijmegen

ZIP/Postal Code

6500HB

Country

Netherlands

12. IPD Sharing Statement

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Insulin by Jet-injection for Hyperglycemia in Diabetes

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