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…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The time in minutes until plasma glucose concentration has dropped with >=10
mmol/l.
Secondary outcome
The time until plasma glucose values drop below 8 and 5 mmol/l, the slope of
the glucose fall, the area under the time-glucose curve from time 0 to 2h and 0
to 6h, (time to) maximal insulin concentration, total duration of
hyperinsulinaemia, area under the insulin concentration curve and time until
50% of insulin absorption.
Background summary
Recently, we showed in both healthy, non-diabetic volunteers and in patients
with type 1 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.
Study objective
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.
Study design
Double-blind double-dummy randomised controlled cross-over
Intervention
The pharmacokinetic and pharmacodynamic profile of insulin aspart will be
derived from the time-action profiles of plasma insulin and glucose,
respectively, in response to subcutaneous injection of 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: on one occasion the
jet-injector will be used to administer insulin and a conventional insulin pen
to inject a placebo solution, whereas on the other occasion insulin will be
injected with the conventional pen and placebo with the jet-injector. The order
of these occasions will be randomised and blinded to both the investigator and
the patient. Both devices will be operated by the patient after sufficient
training. Ease of use will be evaluated.
Study burden and risks
The study is judged to cause only marginal potential risk to the participants.
All participants will undergo a standard physical examination and laboratory
evaluation to determine eligibility. During the two experiments, two cannulae
will be inserted intravenously, one for blood sampling, the other for glucose
20% as needed to prevent hypoglycaemia after insulin injection. A total of 148
ml of blood will be drawn during each experiment for laboratory measurements,
thus 296 ml for the whole study. The risk of hypoglycaemia after insulin
injection is negligible since plasma glucose levels will be measured at
5-10-min intervals and glucose will be infused if glucose levels fall below 4.8
mmol/l. Intravenous glucose may cause local irritation and occasionally
phlebitis. If desired, patients have the opportunity to continue on using the
jet injector for insulin administration.
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Geert Grooteplein 10
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003721-28-NL |
| ClinicalTrials.gov | NCTnummervolgt |
| CCMO | NL46238.091.13 |