To compare the pharmacokinetic and pharmacodynamic profile of the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection to that of the same insulin injected with a conventional pen.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamic parameters: maximal exogenous glucose infusion rate (GIR Cmax)
and time to maximal GIR (GIR Tmax) to maintain euglycaemia, area under the GIR
curve, and time to median GIR (TAUC*).
Secondary outcome
Pharmacokinetic parameters: maximal insulin concentration (Cmax) and time to
maximal insulin concentration (Tmax) after insulin injection, and area under
the insulin concentration curve (AUC).
Background summary
The pharmacological profile of rapid-acting insulin analogues injected
subcutaneously with conventional insulin pens is still far from mimicking the
profile of endogenous insulin release. Insulin injected with a needle-free
jet-injector device may be absorbed faster from the subcutaneous site than
insulin injected with conventional pens.
Study objective
To compare the pharmacokinetic and pharmacodynamic profile of the rapid-acting
insulin analogue aspart (Novorapid®) injected with jet-injection to that of the
same insulin injected with a conventional pen.
Study design
Double-blind randomised controlled cross-over
Intervention
The pharmacokinetic and pharmacodynamic profile of insulin aspart will be
determined with the euglycaemic glucose clamp technique. All participants will
be investigated twice, where on one occasion the jet-injector device will be
used to inject a standardised dose of insulin and a conventional insulin pen to
inject a placebo solution, and 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.
Study burden and risks
All participants will undergo a standard physical examination to determine
eligibility as well as two clamp studies. During the clamps, two cannulae will
be inserted intravenously, one for glucose 20% infusion, the other for blood
sampling. A total of 148 ml of blood will be drawn during each clamp for
laboratory measurements, thus 296 ml for the whole study. Insulin injections
may cause hypoglycaemia, the risk of which is small due to the nature of the
euglycaemic clamp (where continuous glucose infusion is aimed at maintaining
euglycaemia). Intravenous glucose 20% may cause local irritation and
occasionally phlebitis.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for healthy subjects
• Age 18-50 years
• Body-mass index 18-28 kg/m2
• Blood pressure <160/90 mmHg
Inclusion criteria for patients with type 1 diabetes
• Age 18-50 years
• Body-mass index 18-28 kg/m2
• Stable glycaemic control with HbA1c 6.5-9.0%
• Duration of diabetes >1 year
• Blood pressure <160/90 mmHg
Exclusion criteria
Exclusion criteria for healthy subjects
• Inability to provide informed consent
• Chronic use of medication other than oral contraceptives or thyroid hormone replacement therapy (with stable euthyroidism for at least 3 months)
• Type 2 diabetes in first-degree relatives
• History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty)
• Pregnancy
Exclusion criteria for patients with type 1 diabetes
• Inability to provide informed consent
• Chronic use of medication other than insulin, oral contraceptives, thyroid hormone replacement therapy (with stable euthyroidism for at least 3 months), or low-dose angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) treatment
• Macroalbuminuria, i.e. urinary albumin excretion >200 *g/min in collected urine sample or urinary albumin-to-creatinine ratio >300 mg/g in spot urine sample
• Symptomatic diabetic neuropathy
• Proliferative diabetic retinopathy (a history of proliferative retinopathy that was successfully treated with laser coagulopathy is not an exclusion criterion)
• History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty)
• Pregnancy
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 | EUCTR2009-015398-11-NL |
| ClinicalTrials.gov | NCT-nummernognietbekend |
| CCMO | NL29503.091.09 |