Diabetes Mellitus
Conditions
Keywords
diabetes, insulin administration, hyperglycaemia, insulin aspart
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.
Interventions
DRUGinsulin 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) 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.
Sponsors
University Medical Center Nijmegen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T-BG≥10 | participants will be followed for the duration of the study, an expected average of 4 weeks | the time in minutes until plasma glucose concentration has dropped with ≥ 10mmol/l (T-BG≥10). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rfall | participants will be followed for the duration of the study, an expected average of 4 weeks | the slope of the glucose fall (mmol • l-1 • min-1), calculated from the time- glucose curve |
| BG-AUC 0-6h | participants will be followed for the duration of the study, an expected average of 4 weeks | the area under the time-glucose curve (mmol • min-1 • l-1), from 0 to 6h after insulin injection. |
| T-INSBL | participants will be followed for the duration of the study, an expected average of 4 weeks | the time until plasma insulin values drop below baseline values (minutes) |
| INSAUC | participants will be followed for the duration of the study, an expected average of 4 weeks | area under the insulin concentration curve (pmol • min-1 • l-1)(from timepoint 0), reflects total insulin absorption |
| T-INSAUC50% | participants will be followed for the duration of the study, an expected average of 4 weeks | time until 50% of insulin absorption in minutes(mean residence time, MRT) |
| C-INSmax (pmol/l) | participants will be followed for the duration of the study, an expected average of 4 weeks | maximal insulin concentration |
| T-INSmax | participants will be followed for the duration of the study, an expected average of 4 weeks | time to maximal insulin concentration in minutes(C-INSmax) |
| T-BG5 and 8 (min) | participants will be followed for the duration of the study, an expected average of 4 weeks | the time in minutes until plasma glucose values drop below 8 an 5 mmol/l, respectively |
| BG-AUC 0-2h | participants will be followed for the duration of the study, an expected average of 4 weeks | the area under the time-glucose curve, reflecting post-injection hyperglycaemic burden, from 0 to 2h after insulin injection. |
Other
| Measure | Time frame | Description |
|---|---|---|
| exogenous glucose | participants will be followed for the duration of the study, an expected average of 4 weeks | Amount of exogenous glucose required to prevent hypoglycaemia after insulin injection |
| time exogenous glucose requirement | participants will be followed for the duration of the study, an expected average of 4 weeks | Duration of time that exogenous glucose is required to prevent hypoglycaemia after insulin injection. |
| hypoglycaemia | participants will be followed for the duration of the study, an expected average of 4 weeks | Number of patients requiring exogenous glucose infusion to prevent hypoglycaemia (blood glucose ≤3.9 mmol/l) after insulin injection; |
| NRS pain | participants will be followed for the duration of the study, an expected average of 4 weeks | 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) |
Countries
Netherlands
Outcome results
None listed