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 prior to a standardised meal.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Area under the baseline-subtracted plasma glucose concentration time-curve from
time 0 to 2 h after insulin injection and meal ingestion (BG-AUC0-2h)
Secondary outcome
- area under the baseline-subtracted plasma glucose concentration time-curve
from time 0 to 6 h after insulin injection and meal ingestion (BG-AUC0-6h)
- maximal glucose excursion after insulin injection and meal ingestion (BGmax)
- time to maximal glucose excursion after insulin injection and meal ingestion
(T-BGmax)
- time until plasma glucose has returned to baseline values after insulin
injection and meal ingestion (T-BGBL)
- maximal insulin concentration (C-INSmax)
- time to maximal insulin concentration (T-INSmax)
- area under the insulin concentration curve (from timepoint 0) (INSAUC)
- time until 50% of insulin absorption (mean residence time, MRT) (T-INSAUC50%)
- Number of patients requiring exogenous glucose infusion to prevent
postprandial hypoglycaemia after insulin injection and meal ingestion;
- Amount of exogenous glucose required to prevent postprandial hypoglycaemia
after insulin injection and meal ingestion;
- Duration of time that exogenous glucose is required to prevent postprandial
hypoglycaemia after insulin injection and meal ingestion.
Background summary
In a previous study, we showed that absorption and glucose-lowering action of
rapid-acting insulin analogues occurred twice as fast when these analogues were
administered by jet injection technology rather than by conventional insulin
pen in healthy non-diabetic subjects. The pharmacology of rapid-acting insulin
injected by jet injection may provide a more physiological meal insulin
substitution profile than that of conventional insulin 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 prior to a standardised meal.
Study design
Double-blind double-dummy randomised controlled cross-over
Intervention
Subcutaneous injection of aspart insulin by jet injector versus conventional
insulin pen (simultaneous injection of placebo with the comparator pen
according to the dubble-dummy design), directly prior to a standardised test
meal. Subsequently, blood will be drawn at 5-10 minute intervals for the
determination of plasma glucose and insulin values. When plasma glucose levels
tend to drop below 4.8 mmol/l, glucose 20% will be administered intravenously
as required to maintain euglycaemia.
Study burden and risks
All potential participants will need to undergo a standard 30-minute screening
visit to determine eligibility for the study. The experimental days last 10.5
hours per day, excluding commuting time. Prior to the experiments, participants
are asked to adhere to some dietary advice prior to the experiments, to arrive
in fasting condition on the experimental days and to adjust their insulin
accordingly.
On the experimental days, two intravenous lines will be inserted for
administration of insulin and glucose and for blood sampling. Insertion of
these lines can be complicated by local bruises and flebitis. Infusion of
glucose 20% can cause flebitis. Both bruises and flebitis usually recover
without treatment. Insulin carries the risk of hypoglycaemia, but this risk is
negligable because of the frequent determination of the plasma glucose vaules
and the infusion of exogenous glucose when plasma glucose values fall belwow
4.8 mmol/l.
Postbus 9101
6500 HB Nijmgen
NL
Postbus 9101
6500 HB Nijmgen
NL
Listed location countries
Age
Inclusion criteria
•Age 18-70 years
•Body-mass index 18-30 kg/m2
•Stable glycaemic control with HbA1c 6.5-9.0%
•Duration of diabetes >1 year
•Insulin use at least once daily or with subcutaneous pump
•Blood pressure <160/90 mmHg
Exclusion criteria
•Inability to provide informed consent
•Requirement of <8 units of rapid-acting insulin (analogue) before meals
•Chronic use of anticoagulants
•Chronic use of sulphonylurea derivatives, GLP-1 based treatments, acarbose or thiazolidinediones
•Chronic use of three or more blood pressure lowering agents (except thiazide diuretics)
•Treatment with prednisolone, non-steriodal anti-inflammatory drugs (NSAIDs), immunosuppressive agents, cytostatic drugs, hormone therapy except insulin, thyroid supplementation and oral anticonceptives
•Known allergy to aspart insulin
•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 or the intention to become pregnant
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 | EUCTR2011-002306-79-NL |
| CCMO | NL36908.091.11 |
| Other | volgt nog |