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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands
T-BG≥10
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
T-BG5 and 8 (min)
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
Rfall
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
BG-AUC 0-2h
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
BG-AUC 0-6h
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
C-INSmax (pmol/l)
maximal insulin concentration
Time frame: participants will be followed for the duration of the study, an expected average of 4 weeks
T-INSmax
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
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T-INSBL
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
INSAUC
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
T-INSAUC50%
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